diff --git a/MANIFEST.in b/MANIFEST.in
deleted file mode 100644
index bd658b7b9..000000000
--- a/MANIFEST.in
+++ /dev/null
@@ -1,7 +0,0 @@
-include CHANGES.md dtox.sh mypy.ini tox.ini
-graft docker
-graft docs
-graft scripts
-graft testing
-graft tests
-global-exclude *.pyc *.pyo
diff --git a/build-backend/pex_build.dist-info/entry_points.txt b/build-backend/pex_build.dist-info/entry_points.txt
new file mode 100644
index 000000000..7e0169d7f
--- /dev/null
+++ b/build-backend/pex_build.dist-info/entry_points.txt
@@ -0,0 +1,2 @@
+[hatch]
+pex-dynamic-requires-python = pex_build.hatchling.hooks
diff --git a/build-backend/pex_build/__init__.py b/build-backend/pex_build/__init__.py
new file mode 100644
index 000000000..8f221708c
--- /dev/null
+++ b/build-backend/pex_build/__init__.py
@@ -0,0 +1,2 @@
+# Copyright 2024 Pants project contributors (see CONTRIBUTORS.md).
+# Licensed under the Apache License, Version 2.0 (see LICENSE).
diff --git a/build-backend/pex_build/hatchling/__init__.py b/build-backend/pex_build/hatchling/__init__.py
new file mode 100644
index 000000000..8f221708c
--- /dev/null
+++ b/build-backend/pex_build/hatchling/__init__.py
@@ -0,0 +1,2 @@
+# Copyright 2024 Pants project contributors (see CONTRIBUTORS.md).
+# Licensed under the Apache License, Version 2.0 (see LICENSE).
diff --git a/build-backend/pex_build/hatchling/build.py b/build-backend/pex_build/hatchling/build.py
new file mode 100644
index 000000000..e1be4392b
--- /dev/null
+++ b/build-backend/pex_build/hatchling/build.py
@@ -0,0 +1,7 @@
+# Copyright 2024 Pants project contributors (see CONTRIBUTORS.md).
+# Licensed under the Apache License, Version 2.0 (see LICENSE).
+
+from __future__ import absolute_import
+
+# We re-export all hatchling's PEP-517 build backend hooks here for the build frontend to call.
+from hatchling.build import *  # NOQA
diff --git a/build-backend/pex_build/hatchling/dynamic_requires_python.py b/build-backend/pex_build/hatchling/dynamic_requires_python.py
new file mode 100644
index 000000000..d65941fb8
--- /dev/null
+++ b/build-backend/pex_build/hatchling/dynamic_requires_python.py
@@ -0,0 +1,27 @@
+# Copyright 2024 Pants project contributors (see CONTRIBUTORS.md).
+# Licensed under the Apache License, Version 2.0 (see LICENSE).
+
+from __future__ import absolute_import, print_function
+
+import os
+import sys
+from typing import Any, Dict
+
+from hatchling.metadata.plugin.interface import MetadataHookInterface
+
+
+class DynamicRequiresPythonHook(MetadataHookInterface):
+    """Allows dynamically specifying requires-python metadata via _PEX_REQUIRES_PYTHON env var."""
+
+    PLUGIN_NAME = "pex-dynamic-requires-python"
+
+    def update(self, metadata):
+        # type: (Dict[str, Any]) -> None
+        requires_python = os.environ.get("_PEX_REQUIRES_PYTHON")
+        if requires_python:
+            print(
+                "pex_build: Dynamically modifying pyproject.toml requires-python of {original} to "
+                "{dynamic}".format(original=metadata["requires-python"], dynamic=requires_python),
+                file=sys.stderr,
+            )
+            metadata["requires-python"] = requires_python
diff --git a/build-backend/pex_build/hatchling/hooks.py b/build-backend/pex_build/hatchling/hooks.py
new file mode 100644
index 000000000..b11ec0891
--- /dev/null
+++ b/build-backend/pex_build/hatchling/hooks.py
@@ -0,0 +1,15 @@
+# Copyright 2024 Pants project contributors (see CONTRIBUTORS.md).
+# Licensed under the Apache License, Version 2.0 (see LICENSE).
+
+from __future__ import absolute_import
+
+from typing import Type
+
+from hatchling.plugin import hookimpl
+from pex_build.hatchling.dynamic_requires_python import DynamicRequiresPythonHook
+
+
+@hookimpl
+def hatch_register_metadata_hook():
+    # type: () -> Type[DynamicRequiresPythonHook]
+    return DynamicRequiresPythonHook
diff --git a/mypy.ini b/mypy.ini
index 76b0c73fd..a73b47703 100644
--- a/mypy.ini
+++ b/mypy.ini
@@ -45,3 +45,10 @@ ignore_missing_imports = True
 
 [mypy-pkg_resources]
 ignore_missing_imports = True
+
+[mypy-hatchling.*]
+# Currently we use one venv for MyPy checks and the hatchling requirements are not compatible with
+# the rest; so we ignore. Ideally pex.hatchling build backend type-checking would be segregated as
+# scripts are today and each with its own venv.
+ignore_missing_imports = True
+
diff --git a/pex/pip/tool.py b/pex/pip/tool.py
index 2c189224a..90be6a305 100644
--- a/pex/pip/tool.py
+++ b/pex/pip/tool.py
@@ -436,6 +436,7 @@ def spawn_download_distributions(
 
         download_cmd = ["download", "--dest", download_dir]
         extra_env = {}  # type: Dict[str, str]
+        pex_extra_sys_path = []  # type: List[str]
 
         if not build:
             download_cmd.extend(["--only-binary", ":all:"])
@@ -451,7 +452,7 @@ def spawn_download_distributions(
 
         if not build_isolation:
             download_cmd.append("--no-build-isolation")
-            extra_env.update(PEP517_BACKEND_PATH=os.pathsep.join(sys.path))
+            pex_extra_sys_path.extend(sys.path)
 
         if allow_prereleases:
             download_cmd.append("--pre")
@@ -483,7 +484,6 @@ def spawn_download_distributions(
             )
 
         log_analyzers = []  # type: List[LogAnalyzer]
-        pex_extra_sys_path = []  # type: List[str]
         for obs in (foreign_platform_observer, observer):
             if obs:
                 if obs.analyzer:
@@ -492,10 +492,10 @@ def spawn_download_distributions(
                 extra_sys_path = obs.patch_set.emit_patches(package=self._PATCHES_PACKAGE_NAME)
                 if extra_sys_path:
                     pex_extra_sys_path.append(extra_sys_path)
+                    extra_env[self._PATCHES_PACKAGE_ENV_VAR_NAME] = self._PATCHES_PACKAGE_NAME
 
         if pex_extra_sys_path:
             extra_env["PEX_EXTRA_SYS_PATH"] = os.pathsep.join(pex_extra_sys_path)
-            extra_env[self._PATCHES_PACKAGE_ENV_VAR_NAME] = self._PATCHES_PACKAGE_NAME
 
         # The Pip 2020 resolver hides useful dependency conflict information in stdout interspersed
         # with other information we want to suppress. We jump though some hoops here to get at that
@@ -624,7 +624,7 @@ def spawn_build_wheels(
         if not build_isolation:
             wheel_cmd.append("--no-build-isolation")
             interpreter = interpreter or PythonInterpreter.get()
-            extra_env.update(PEP517_BACKEND_PATH=os.pathsep.join(interpreter.sys_path))
+            extra_env.update(PEX_EXTRA_SYS_PATH=os.pathsep.join(interpreter.sys_path))
 
         if not verify:
             wheel_cmd.append("--no-verify")
diff --git a/pex/vendor/__init__.py b/pex/vendor/__init__.py
index 35131734d..caf648681 100644
--- a/pex/vendor/__init__.py
+++ b/pex/vendor/__init__.py
@@ -151,14 +151,7 @@ def create_packages(self):
         if not self.rewrite:
             # The extra package structure is only required by Pex for vendored code used via import
             # rewrites.
-
-            # N.B.: Although we've historically early-returned here, the switch from flit to
-            # setuptools for our build backend necessitates all vendored dists are seen as part of
-            # the `pex` package tree by setuptools to get all vendored code properly included in
-            # our distribution.
-            # TODO(John Sirois): re-introduce early return once it is no longer foils our build
-            #  process.
-            pass
+            return
 
         for index, _ in enumerate(self._subpath_components):
             relpath = _PACKAGE_COMPONENTS + self._subpath_components[: index + 1] + ["__init__.py"]
diff --git a/pex/vendor/_vendored/pip/.layout.json b/pex/vendor/_vendored/pip/.layout.json
index f58938501..9c0d6c183 100644
--- a/pex/vendor/_vendored/pip/.layout.json
+++ b/pex/vendor/_vendored/pip/.layout.json
@@ -1 +1 @@
-{"fingerprint": "69c1ee1f3c238f9f7a88645a63f68c3c5802b6e3d349612fde5fe2b8c692a668", "record_relpath": "pip-20.3.4.dist-info/RECORD", "stash_dir": ".prefix"}
\ No newline at end of file
+{"fingerprint": "120267325b80f5c4b4adac019eb6617ab3319395c043d2871eedf70dd6ae2954", "record_relpath": "pip-20.3.4.dist-info/RECORD", "stash_dir": ".prefix"}
\ No newline at end of file
diff --git a/pex/vendor/_vendored/pip/__init__.py b/pex/vendor/_vendored/pip/__init__.py
deleted file mode 100644
index e69de29bb..000000000
diff --git a/pyproject.toml b/pyproject.toml
index 1b734fee2..29889539c 100644
--- a/pyproject.toml
+++ b/pyproject.toml
@@ -1,9 +1,76 @@
 [build-system]
-# N.B.: We use `setup.cfg` for declarative metadata instead of `[project]` here since support for
-# pyproject.toml projects was introduced in setuptools 61.0.0 which only supports Python>=3.7. We
-# need to also support 2.7, 3.5 and 3.6.
-requires = ["setuptools"]
-build-backend = "setuptools.build_meta"
+# N.B.: We use an in-tree backend just to get our hatchling in-tree plugins visible without having
+# to publish a plugin distribution. The real backend is `hatchling.build` and the
+# `pex_build.hatchling.build` backend is a very thin wrapper that just serves to install our hooks
+# just in time.
+backend-path = ["build-backend"]
+build-backend = "pex_build.hatchling.build"
+requires = ["hatchling"]
+
+[tool.hatch.metadata.hooks.pex-dynamic-requires-python]
+# We need this empty table to enable our hook.
+
+[project]
+name = "pex"
+dynamic = ["version"]
+requires-python = ">=2.7,<3.13,!=3.0.*,!=3.1.*,!=3.2.*,!=3.3.*,!=3.4.*"
+authors = [
+  {name = "The PEX developers", email="pantsbuild@gmail.com"}
+]
+description = "The PEX packaging toolchain."
+readme = "README.rst"
+license-files = { paths = ["LICENSE"] }
+keywords = ["package", "executable", "virtualenv", "lock", "freeze"]
+classifiers = [
+  "Development Status :: 5 - Production/Stable",
+  "Intended Audience :: Developers",
+  "License :: OSI Approved :: Apache Software License",
+  "Operating System :: Unix",
+  "Operating System :: POSIX :: Linux",
+  "Operating System :: MacOS :: MacOS X",
+  "Programming Language :: Python",
+  "Programming Language :: Python :: 2",
+  "Programming Language :: Python :: 2.7",
+  "Programming Language :: Python :: 3",
+  "Programming Language :: Python :: 3.5",
+  "Programming Language :: Python :: 3.6",
+  "Programming Language :: Python :: 3.7",
+  "Programming Language :: Python :: 3.8",
+  "Programming Language :: Python :: 3.9",
+  "Programming Language :: Python :: 3.10",
+  "Programming Language :: Python :: 3.11",
+  "Programming Language :: Python :: 3.12",
+  "Programming Language :: Python :: Implementation :: CPython",
+  "Programming Language :: Python :: Implementation :: PyPy",
+  "Topic :: Software Development :: Build Tools",
+  "Topic :: System :: Archiving :: Packaging",
+  "Topic :: System :: Software Distribution",
+  "Topic :: Utilities",
+]
+
+[project.optional-dependencies]
+subprocess = [
+  "subprocess32>=3.2.7; python_version < '3'"
+]
+
+[project.scripts]
+pex = "pex.bin.pex:main"
+pex3 = "pex.cli.pex:main"
+pex-tools = "pex.tools.main:main"
+
+[project.entry-points."distutils.commands"]
+bdist_pex = "pex.distutils.commands.bdist_pex:bdist_pex"
+
+[project.urls]
+Homepage = "https://github.com/pantsbuild/pex"
+Download = "https://github.com/pantsbuild/pex/releases/latest/download/pex"
+Changelog = "https://github.com/pantsbuild/pex/blob/main/CHANGES.md"
+Documentation = "https://pex.readthedocs.io/en/latest/"
+Source = "https://github.com/pantsbuild/pex"
+
+[tool.hatch.version]
+path = "pex/version.py"
+pattern = '__version__ = "(?P<version>[^"]+)"'
 
 [tool.black]
 line-length = 100
diff --git a/scripts/format.py b/scripts/format.py
index f71abf756..ba7629894 100755
--- a/scripts/format.py
+++ b/scripts/format.py
@@ -35,7 +35,7 @@ def run_black(*args: str) -> None:
         dest=sys.stdout,
     ) as out_fd:
         subprocess.run(
-            args=["black", "--color", *args, "setup.py", "pex", "scripts", "testing", "tests"],
+            args=["black", "--color", *args, "build-backend", "pex", "scripts", "testing", "tests"],
             stdout=out_fd,
             stderr=subprocess.STDOUT,
             check=True,
@@ -44,7 +44,7 @@ def run_black(*args: str) -> None:
 
 def run_isort(*args: str) -> None:
     subprocess.run(
-        args=["isort", *args, "setup.py", "pex", "scripts", "testing", "tests"], check=True
+        args=["isort", *args, "build-backend", "pex", "scripts", "testing", "tests"], check=True
     )
 
 
diff --git a/scripts/lint.py b/scripts/lint.py
index 794643fc3..41e01ec20 100644
--- a/scripts/lint.py
+++ b/scripts/lint.py
@@ -24,7 +24,7 @@ def run_autoflake(*args: str) -> None:
             "--exclude",
             ",".join(excludes),
             "--recursive",
-            "setup.py",
+            "build-backend",
             "pex",
             "scripts",
             "testing",
diff --git a/scripts/package.py b/scripts/package.py
index 50f55076e..b160f78bc 100755
--- a/scripts/package.py
+++ b/scripts/package.py
@@ -6,6 +6,7 @@
 import subprocess
 import sys
 from argparse import ArgumentDefaultsHelpFormatter, ArgumentParser
+from email.parser import Parser
 from enum import Enum, unique
 from http.server import HTTPServer, SimpleHTTPRequestHandler
 from pathlib import Path, PurePath
@@ -46,7 +47,12 @@ def build_pex_pex(output_file: PurePath, verbosity: int = 0) -> None:
     subprocess.run(args, check=True)
 
 
-def describe_git_rev() -> str:
+def describe_rev() -> str:
+    if not os.path.isdir(".git") and os.path.isfile("PKG-INFO"):
+        # We're being build from an unpacked sdist.
+        with open("PKG-INFO") as fp:
+            return Parser().parse(fp).get("Version", "Unknown Version")
+
     git_describe = subprocess.run(
         ["git", "describe"], check=True, stdout=subprocess.PIPE, encoding="utf-8"
     )
@@ -103,9 +109,9 @@ def main(
         print(f"Building Pex PEX to `{pex_output_file}` ...")
         build_pex_pex(pex_output_file, verbosity)
 
-        git_rev = describe_git_rev()
+        rev = describe_rev()
         sha256, size = describe_file(pex_output_file)
-        print(f"Built Pex PEX @ {git_rev}:")
+        print(f"Built Pex PEX @ {rev}:")
         print(f"sha256: {sha256}")
         print(f"  size: {size}")
 
diff --git a/scripts/typecheck.py b/scripts/typecheck.py
index fd2d33c13..f3e2ad93c 100755
--- a/scripts/typecheck.py
+++ b/scripts/typecheck.py
@@ -38,6 +38,9 @@ def run_mypy(python_version: str, files: Sequence[str], subject: str = "files")
 
 
 def main() -> None:
+    run_mypy(
+        "2.7", files=sorted(find_files_to_check(include=["build-backend"])), subject="build-backend"
+    )
     run_mypy("3.8", files=sorted(find_files_to_check(include=["scripts"])), subject="scripts")
 
     source_and_tests = sorted(
diff --git a/setup.cfg b/setup.cfg
deleted file mode 100644
index 37f9ecc4f..000000000
--- a/setup.cfg
+++ /dev/null
@@ -1,91 +0,0 @@
-[metadata]
-name = pex
-version = attr: pex.version.__version__
-author = The PEX developers
-author_email = pantsbuild@gmail.com
-description = The PEX packaging toolchain.
-long_description = file: README.rst
-keywords = package, executable, virtualenv, lock, freeze
-url = https://github.com/pantsbuild/pex
-download_url = https://github.com/pantsbuild/pex/releases/latest/download/pex
-project_urls =
-    Changelog = https://github.com/pantsbuild/pex/blob/main/CHANGES.md
-    Documentation = https://pex.readthedocs.io/en/latest/
-license_file = LICENSE
-classifiers =
-    Development Status :: 5 - Production/Stable
-    Intended Audience :: Developers
-    License :: OSI Approved :: Apache Software License
-    Operating System :: Unix
-    Operating System :: POSIX :: Linux
-    Operating System :: MacOS :: MacOS X
-    Programming Language :: Python
-    Programming Language :: Python :: 2
-    Programming Language :: Python :: 2.7
-    Programming Language :: Python :: 3
-    Programming Language :: Python :: 3.5
-    Programming Language :: Python :: 3.6
-    Programming Language :: Python :: 3.7
-    Programming Language :: Python :: 3.8
-    Programming Language :: Python :: 3.9
-    Programming Language :: Python :: 3.10
-    Programming Language :: Python :: 3.11
-    Programming Language :: Python :: 3.12
-    Programming Language :: Python :: Implementation :: CPython
-    Programming Language :: Python :: Implementation :: PyPy
-    Topic :: Software Development :: Build Tools
-    Topic :: System :: Archiving :: Packaging
-    Topic :: System :: Software Distribution
-    Topic :: Utilities
-
-[options]
-zip_safe = False
-include_package_data = False
-packages = find:
-python_requires = >=2.7,<3.13,!=3.0.*,!=3.1.*,!=3.2.*,!=3.3.*,!=3.4.*
-
-[options.entry_points]
-console_scripts =
-    pex = pex.bin.pex:main
-    pex3 = pex.cli.pex:main
-    pex-tools = pex.tools.main:main
-
-distutils.commands =
-    bdist_pex = pex.distutils.commands.bdist_pex:bdist_pex
-
-[options.extras_require]
-# For improved subprocess robustness under python2.7.
-subprocess =
-    subprocess32>=3.2.7; python_version < "3"
-
-[options.packages.find]
-include =
-    pex
-    pex.*
-
-# We use `[options] include_package_data = False` above and manually include package data here to
-# avoid picking up `pex.egg-info/*` temporary build metadata in the final sdist, which leads to
-# non-reproducible builds and resulting test failures. When using
-# `[options] include_package_data = True`, older setuptools (python 2.7, 3.5 and 3.6 are affected)
-# demands the build dirs we pass in `setup.py` be relative instead of absolute, but this comes with
-# no way to turn off inclusion of the `pex.egg-info/*` which then is in-tree with the `pex` package
-# source root. The relative path restriction in old setuptools is lifted though when
-# `[options] include_package_data = False` at the cost of manually needing to specify package data
-# includes here. An important detail in specifying those includes is that `**` syntax supported by
-# newer setuptools also cannot be used (it does not cause an error, but also does not pick up the
-# right files when building the sdist). As a result we use a clunkier, more manual, set of include
-# patterns here than we would otherwise need if we could leverage `**` support.
-[options.package_data]
-* =
-    .layout.json
-    .prefix/bin/*
-    *
-    *.dist-info/*
-
-[options.exclude_package_data]
-* =
-    *.pyc
-    *.pyo
-
-[bdist_wheel]
-universal = True
diff --git a/setup.py b/setup.py
deleted file mode 100644
index d0bcf30a4..000000000
--- a/setup.py
+++ /dev/null
@@ -1,44 +0,0 @@
-# Copyright 2024 Pants project contributors (see CONTRIBUTORS.md).
-# Licensed under the Apache License, Version 2.0 (see LICENSE).
-
-import atexit
-import os
-import shutil
-import tempfile
-
-from setuptools import setup  # type: ignore[import]  # The Python 2.7 type check can't see this.
-
-_BUILD_DIR = None
-
-
-def ensure_unique_build_dir():
-    # type: () -> str
-    global _BUILD_DIR
-    if _BUILD_DIR is None:
-        _build_dir = tempfile.mkdtemp(prefix="pex-dist-build.")
-        atexit.register(shutil.rmtree, _build_dir, ignore_errors=True)
-        _BUILD_DIR = _build_dir
-    return _BUILD_DIR
-
-
-def unique_build_dir(name):
-    # type: (str) -> str
-    path = os.path.join(ensure_unique_build_dir(), name)
-    os.mkdir(path)
-    return path
-
-
-if __name__ == "__main__":
-    setup(
-        # The `egg_info --egg-base`, `build --build-base` and `bdist_wheel --bdist-dir` setup.py
-        # sub-command options we pass below work around the otherwise default `<CWD>/build/`
-        # directory for all three which defeats concurrency in tests.
-        options={
-            "egg_info": {"egg_base": unique_build_dir("egg_base")},
-            "build": {"build_base": unique_build_dir("build_base")},
-            "bdist_wheel": {"bdist_dir": unique_build_dir("bdist_dir")},
-        },
-        # This supports expanding the supported Python range via the _PEX_REQUIRES_PYTHON env var
-        # for testing unreleased Pythons.
-        python_requires=os.environ.get("_PEX_REQUIRES_PYTHON"),
-    )
diff --git a/tests/bin/test_sh_boot.py b/tests/bin/test_sh_boot.py
index e191416ae..fa5b3d08b 100644
--- a/tests/bin/test_sh_boot.py
+++ b/tests/bin/test_sh_boot.py
@@ -6,7 +6,6 @@
 import pytest
 
 from pex import sh_boot
-from pex.compatibility import ConfigParser
 from pex.interpreter import PythonInterpreter
 from pex.interpreter_constraints import InterpreterConstraints, iter_compatible_versions
 from pex.orderedset import OrderedSet
@@ -20,6 +19,10 @@
 if TYPE_CHECKING:
     from typing import Iterable, List
 
+    import toml  # vendor:skip
+else:
+    from pex.third_party import toml
+
 
 def calculate_binary_names(
     targets=Targets(),  # type: Targets
@@ -39,9 +42,10 @@ def requires_python(pex_project_dir):
     requires_python = os.environ.get("_PEX_REQUIRES_PYTHON")
     if requires_python:
         return requires_python
-    parser = ConfigParser()
-    parser.read(os.path.join(pex_project_dir, "setup.cfg"))
-    return cast(str, parser.get("options", "python_requires")).strip()
+    return cast(
+        str,
+        toml.load(os.path.join(pex_project_dir, "pyproject.toml"))["project"]["requires-python"],
+    )
 
 
 def expected(
diff --git a/tests/build_system/test_pep_518.py b/tests/build_system/test_pep_518.py
index 19f01f8f6..0a129f61a 100644
--- a/tests/build_system/test_pep_518.py
+++ b/tests/build_system/test_pep_518.py
@@ -68,14 +68,15 @@ def test_load_build_system_pyproject(
 
     build_system = load_build_system(pex_project_dir)
     assert isinstance(build_system, BuildSystem)
-    assert "setuptools.build_meta" == build_system.build_backend
+    assert "pex_build.hatchling.build" == build_system.build_backend
     dists = {
         dist.metadata.project_name
         for dist in Virtualenv(build_system.venv_pex.venv_dir).iter_distributions()
     }
-    assert ProjectName("setuptools") in dists
+    assert ProjectName("hatchling") in dists
     subprocess.check_call(
-        args=[build_system.venv_pex.pex, "-c", "import {}".format(build_system.build_backend)]
+        args=[build_system.venv_pex.pex, "-c", "import {}".format(build_system.build_backend)],
+        env=build_system.env,
     )
 
 
diff --git a/tests/integration/build_system/test_pep_518.py b/tests/integration/build_system/test_pep_518.py
index d538f43ae..c90199802 100644
--- a/tests/integration/build_system/test_pep_518.py
+++ b/tests/integration/build_system/test_pep_518.py
@@ -55,5 +55,6 @@ def test_load_build_system_pyproject_custom_repos(
     build_system = load_build_system(current_target, custom_resolver, pex_project_dir)
     assert isinstance(build_system, BuildSystem)
     subprocess.check_call(
-        args=[build_system.venv_pex.pex, "-c", "import {}".format(build_system.build_backend)]
+        args=[build_system.venv_pex.pex, "-c", "import {}".format(build_system.build_backend)],
+        env=build_system.env,
     )
diff --git a/tests/integration/test_issue_1232.py b/tests/integration/test_issue_1232.py
index 9a13280e4..0521db026 100644
--- a/tests/integration/test_issue_1232.py
+++ b/tests/integration/test_issue_1232.py
@@ -79,16 +79,11 @@ def vendored_toplevel(isolated_dir):
     shutil.copytree("pex", os.path.join(modified_pex_src, "pex"))
     with open(os.path.join(modified_pex_src, "pex", "version.py"), "a") as fp:
         fp.write("# modified\n")
-    # N.B.: README.rst and LICENSE are needed by the build process: we configure our PEP-517 project
-    # to use these files for the project distribution and license respectively.
-    for build_file in (
-        "pyproject.toml",
-        "setup.cfg",
-        "setup.py",
-        "MANIFEST.in",
-        "README.rst",
-        "LICENSE",
-    ):
+    # N.B.: build-backend/, README.rst and LICENSE are needed by the build process: we configure
+    # our PEP-517 project to use these paths for the in-tree build backend, distribution readme
+    # and distribution license respectively.
+    shutil.copytree("build-backend", os.path.join(modified_pex_src, "build-backend"))
+    for build_file in ("pyproject.toml", "README.rst", "LICENSE"):
         shutil.copy(build_file, os.path.join(modified_pex_src, build_file))
 
     modified_pex = os.path.join(str(tmpdir), "modified.pex")
diff --git a/tests/integration/test_issue_1560.py b/tests/integration/test_issue_1560.py
index f9ece4900..70a4cb16c 100644
--- a/tests/integration/test_issue_1560.py
+++ b/tests/integration/test_issue_1560.py
@@ -40,13 +40,13 @@ def test_build_isolation(
     subprocess.check_call(args=[pip, "uninstall", "-y"] + build_requirements)
     result = run_pex_command(args=[pex_project_dir, "--no-build-isolation"], python=python)
     result.assert_failure()
-    assert "raise BackendInvalid(" in result.error, (
+    assert "ModuleNotFoundError: " in result.error, (
         "With build isolation turned off, it's expected that any build requirements "
-        "(setuptools for Pex) are pre-installed. They are not; so we expect a failure here."
+        "(setuptools for Pex) are pre-installed. They are not; so we expect a failure here. Got:\n"
+        "{error}".format(error=result.error)
     )
 
-    # N.B.: We need wheel so that setuptools.build_meta can execute bdist_wheel successfully.
-    subprocess.check_call(args=[pip, "install", "wheel"] + build_requirements)
+    subprocess.check_call(args=[pip, "install"] + build_requirements)
 
     pex = os.path.join(str(tmpdir), "pex")
     run_pex_command(
diff --git a/tox.ini b/tox.ini
index 516a3ff3e..5cdd7455e 100644
--- a/tox.ini
+++ b/tox.ini
@@ -7,6 +7,13 @@ requires =
     tox<4
     virtualenv<20.16
 
+[tox:.package]
+# N.B.: tox will use the same python version as under what tox is installed to package, so unless
+# this is python 3 you can require a given python version for the packaging environment via the
+# basepython key. We need this for hatchling which only runs under python3 but works for python2
+# projects.
+basepython = python3
+
 [testenv]
 # N.B.: We need modern setuptools downloaded out of band by virtualenv to work with Python>=3.12.
 # Trying to upgrade via Pip is too late and Pip blows up.
@@ -32,6 +39,8 @@ passenv =
     _PEX_TEST_DEV_ROOT
     # This allows increasing pexpect read timeouts in CI.
     _PEX_PEXPECT_TIMEOUT
+    # This allows experimenting with Requires-Python metadata adjustment.
+    _PEX_REQUIRES_PYTHON
     # These are to support directing test environments to the correct headers on OSX.
     CPATH
     CPPFLAGS