diff --git a/crates/uv/src/commands/project/run.rs b/crates/uv/src/commands/project/run.rs
index 8f8cb7185bc8..a0d040aad585 100644
--- a/crates/uv/src/commands/project/run.rs
+++ b/crates/uv/src/commands/project/run.rs
@@ -25,7 +25,7 @@ use uv_python::{
 };
 use uv_requirements::{RequirementsSource, RequirementsSpecification};
 use uv_scripts::Pep723Script;
-use uv_warnings::warn_user_once;
+use uv_warnings::warn_user;
 use uv_workspace::{DiscoveryOptions, VirtualProject, Workspace, WorkspaceError};
 
 use crate::commands::pip::loggers::{
@@ -111,11 +111,15 @@ pub(crate) async fn run(
             .and_then(PythonVersionFile::into_version)
         {
             Some(request)
-            // (3) `Requires-Python` in `pyproject.toml`
+            // (3) `Requires-Python` in the script
         } else {
-            script.metadata.requires_python.map(|requires_python| {
-                PythonRequest::Version(VersionRequest::Range(requires_python))
-            })
+            script
+                .metadata
+                .requires_python
+                .as_ref()
+                .map(|requires_python| {
+                    PythonRequest::Version(VersionRequest::Range(requires_python.clone()))
+                })
         };
 
         let client_builder = BaseClientBuilder::new()
@@ -134,6 +138,16 @@ pub(crate) async fn run(
         .await?
         .into_interpreter();
 
+        if let Some(requires_python) = script.metadata.requires_python.as_ref() {
+            if !requires_python.contains(interpreter.python_version()) {
+                warn_user!(
+                    "Python {} does not satisfy the script's `requires-python` specifier: `{}`",
+                    interpreter.python_version(),
+                    requires_python
+                );
+            }
+        }
+
         // Install the script requirements, if necessary. Otherwise, use an isolated environment.
         if let Some(dependencies) = script.metadata.dependencies {
             // // Collect any `tool.uv.sources` from the script.
@@ -224,28 +238,28 @@ pub(crate) async fn run(
             );
         }
         if !extras.is_empty() {
-            warn_user_once!("Extras are not supported for Python scripts with inline metadata");
+            warn_user!("Extras are not supported for Python scripts with inline metadata");
         }
         if !dev {
-            warn_user_once!("`--no-dev` is not supported for Python scripts with inline metadata");
+            warn_user!("`--no-dev` is not supported for Python scripts with inline metadata");
         }
         if package.is_some() {
-            warn_user_once!(
+            warn_user!(
                 "`--package` is a no-op for Python scripts with inline metadata, which always run in isolation"
             );
         }
         if locked {
-            warn_user_once!(
+            warn_user!(
                 "`--locked` is a no-op for Python scripts with inline metadata, which always run in isolation"
             );
         }
         if frozen {
-            warn_user_once!(
+            warn_user!(
                 "`--frozen` is a no-op for Python scripts with inline metadata, which always run in isolation"
             );
         }
         if isolated {
-            warn_user_once!(
+            warn_user!(
                 "`--isolated` is a no-op for Python scripts with inline metadata, which always run in isolation"
             );
         }
@@ -293,30 +307,30 @@ pub(crate) async fn run(
         if no_project {
             // If the user ran with `--no-project` and provided a project-only setting, warn.
             if !extras.is_empty() {
-                warn_user_once!("Extras have no effect when used alongside `--no-project`");
+                warn_user!("Extras have no effect when used alongside `--no-project`");
             }
             if !dev {
-                warn_user_once!("`--no-dev` has no effect when used alongside `--no-project`");
+                warn_user!("`--no-dev` has no effect when used alongside `--no-project`");
             }
             if locked {
-                warn_user_once!("`--locked` has no effect when used alongside `--no-project`");
+                warn_user!("`--locked` has no effect when used alongside `--no-project`");
             }
             if frozen {
-                warn_user_once!("`--frozen` has no effect when used alongside `--no-project`");
+                warn_user!("`--frozen` has no effect when used alongside `--no-project`");
             }
         } else if project.is_none() {
             // If we can't find a project and the user provided a project-only setting, warn.
             if !extras.is_empty() {
-                warn_user_once!("Extras have no effect when used outside of a project");
+                warn_user!("Extras have no effect when used outside of a project");
             }
             if !dev {
-                warn_user_once!("`--no-dev` has no effect when used outside of a project");
+                warn_user!("`--no-dev` has no effect when used outside of a project");
             }
             if locked {
-                warn_user_once!("`--locked` has no effect when used outside of a project");
+                warn_user!("`--locked` has no effect when used outside of a project");
             }
             if frozen {
-                warn_user_once!("`--frozen` has no effect when used outside of a project");
+                warn_user!("`--frozen` has no effect when used outside of a project");
             }
         }
 
diff --git a/crates/uv/tests/run.rs b/crates/uv/tests/run.rs
index ffa5261acfca..ee0d30f10a78 100644
--- a/crates/uv/tests/run.rs
+++ b/crates/uv/tests/run.rs
@@ -386,6 +386,68 @@ fn run_pep723_script() -> Result<()> {
     Ok(())
 }
 
+#[test]
+fn run_pep723_script_requires_python() -> Result<()> {
+    let context = TestContext::new_with_versions(&["3.8", "3.11"]);
+
+    // If we have a `.python-version` that's incompatible with the script, we should error.
+    let python_version = context.temp_dir.child(PYTHON_VERSION_FILENAME);
+    python_version.write_str("3.8")?;
+
+    // If the script contains a PEP 723 tag, we should install its requirements.
+    let test_script = context.temp_dir.child("main.py");
+    test_script.write_str(indoc! { r#"
+        # /// script
+        # requires-python = ">=3.11"
+        # dependencies = [
+        #   "iniconfig",
+        # ]
+        # ///
+
+        import iniconfig
+
+        x: str | int = "hello"
+        print(x)
+       "#
+    })?;
+
+    uv_snapshot!(context.filters(), context.run().arg("main.py"), @r###"
+    success: false
+    exit_code: 1
+    ----- stdout -----
+
+    ----- stderr -----
+    Reading inline script metadata from: main.py
+    warning: Python 3.8.[X] does not satisfy the script's `requires-python` specifier: `>=3.11`
+    Resolved 1 package in [TIME]
+    Prepared 1 package in [TIME]
+    Installed 1 package in [TIME]
+     + iniconfig==2.0.0
+    Traceback (most recent call last):
+      File "main.py", line 10, in <module>
+        x: str | int = "hello"
+    TypeError: unsupported operand type(s) for |: 'type' and 'type'
+    "###);
+
+    // Delete the `.python-version` file to allow the script to run.
+    fs_err::remove_file(&python_version)?;
+
+    uv_snapshot!(context.filters(), context.run().arg("main.py"), @r###"
+    success: true
+    exit_code: 0
+    ----- stdout -----
+    hello
+
+    ----- stderr -----
+    Reading inline script metadata from: main.py
+    Resolved 1 package in [TIME]
+    Installed 1 package in [TIME]
+     + iniconfig==2.0.0
+    "###);
+
+    Ok(())
+}
+
 /// Run a `.pyw` script. The script should be executed with `pythonw.exe`.
 #[test]
 #[cfg(windows)]