diff --git a/newsfragments/5343.bugfix.rst b/newsfragments/5343.bugfix.rst
new file mode 100644
index 0000000000..a0d67bfc71
--- /dev/null
+++ b/newsfragments/5343.bugfix.rst
@@ -0,0 +1,4 @@
+A ``long_description`` or ``python_requires`` given in ``setup.py`` while
+``pyproject.toml`` does not list ``readme`` or ``requires-python`` in
+``dynamic`` is now ignored with a warning, as for other fields, instead of
+crashing the build.
diff --git a/setuptools/config/_apply_pyprojecttoml.py b/setuptools/config/_apply_pyprojecttoml.py
index 286ed43cb8..b9d650ddb6 100644
--- a/setuptools/config/_apply_pyprojecttoml.py
+++ b/setuptools/config/_apply_pyprojecttoml.py
@@ -174,11 +174,14 @@ def _guess_content_type(file: str) -> str | None:
 
 
 def _long_description(
-    dist: Distribution, val: _ProjectReadmeValue, root_dir: StrPath | None
+    dist: Distribution, val: _ProjectReadmeValue | None, root_dir: StrPath | None
 ):
     from setuptools.config import expand
 
     file: str | tuple[()]
+    if val is None:  # reset by _handle_missing_dynamic
+        _set_config(dist, "long_description", None)
+        return
     if isinstance(val, str):
         file = val
         text = expand.read_files(file, root_dir)
@@ -247,7 +250,12 @@ def _project_urls(dist: Distribution, val: dict, _root_dir: StrPath | None):
     _set_config(dist, "project_urls", val)
 
 
-def _python_requires(dist: Distribution, val: str, _root_dir: StrPath | None):
+def _python_requires(dist: Distribution, val: str | None, _root_dir: StrPath | None):
+    if val is None:  # reset by _handle_missing_dynamic
+        dist.python_requires = None
+        # _core_metadata writes Requires-Python whenever the attribute exists
+        vars(dist.metadata).pop("python_requires", None)
+        return
     _set_config(dist, "python_requires", _static.SpecifierSet(val))
 
 
diff --git a/setuptools/tests/config/test_apply_pyprojecttoml.py b/setuptools/tests/config/test_apply_pyprojecttoml.py
index 202f23189a..f46519a7e3 100644
--- a/setuptools/tests/config/test_apply_pyprojecttoml.py
+++ b/setuptools/tests/config/test_apply_pyprojecttoml.py
@@ -613,6 +613,8 @@ def pyproject(self, tmp_path, dynamic, extra_content=""):
                 marks=[pytest.mark.filterwarnings("ignore:.*license. overwritten")],
             ),
             ("classifiers", "classifiers", ["Private :: Classifier"]),
+            ("long_description", "readme", "Some description"),
+            ("python_requires", "requires-python", ">=3.8"),
             ("entry_points", "scripts", {"console_scripts": ["foobar=foobar:main"]}),
             ("entry_points", "gui-scripts", {"gui_scripts": ["bazquux=bazquux:main"]}),
             pytest.param(