diff --git a/src/Cli/dotnet/Commands/Run/CSharpCompilerCommand.cs b/src/Cli/dotnet/Commands/Run/CSharpCompilerCommand.cs
index 84ac2b073fe0..f4a4bc902973 100644
--- a/src/Cli/dotnet/Commands/Run/CSharpCompilerCommand.cs
+++ b/src/Cli/dotnet/Commands/Run/CSharpCompilerCommand.cs
@@ -142,6 +142,17 @@ static int ProcessBuildResponse(BuildResponse response, out bool fallbackToNorma
             {
                 case CompletedBuildResponse completed:
                     Reporter.Verbose.WriteLine("Compiler server processed compilation.");
+
+                    // Check if the compilation failed with CS0006 error (metadata file not found).
+                    // This can happen when NuGet cache is cleared and referenced DLLs (e.g., analyzers or libraries) are missing.
+                    if (completed.ReturnCode != 0 && completed.Output.Contains("error CS0006:", StringComparison.Ordinal))
+                    {
+                        Reporter.Verbose.WriteLine("CS0006 error detected in fast compilation path, falling back to full MSBuild.");
+                        Reporter.Verbose.Write(completed.Output);
+                        fallbackToNormalBuild = true;
+                        return completed.ReturnCode;
+                    }
+
                     Reporter.Output.Write(completed.Output);
                     fallbackToNormalBuild = false;
                     return completed.ReturnCode;
diff --git a/src/Cli/dotnet/Commands/Run/VirtualProjectBuildingCommand.cs b/src/Cli/dotnet/Commands/Run/VirtualProjectBuildingCommand.cs
index c6ab42bbc498..7b47b5b6762d 100644
--- a/src/Cli/dotnet/Commands/Run/VirtualProjectBuildingCommand.cs
+++ b/src/Cli/dotnet/Commands/Run/VirtualProjectBuildingCommand.cs
@@ -244,11 +244,6 @@ public override int Execute()
 
                 if (buildLevel is BuildLevel.Csc)
                 {
-                    if (binaryLogger is not null)
-                    {
-                        Reporter.Output.WriteLine(CliCommandStrings.NoBinaryLogBecauseRunningJustCsc.Yellow());
-                    }
-
                     MarkBuildStart();
 
                     // Execute CSC.
@@ -269,6 +264,11 @@ public override int Execute()
                             MarkBuildSuccess(cache);
                         }
 
+                        if (binaryLogger is not null)
+                        {
+                            Reporter.Output.WriteLine(CliCommandStrings.NoBinaryLogBecauseRunningJustCsc.Yellow());
+                        }
+
                         return result;
                     }
 
diff --git a/test/dotnet.Tests/CommandTests/Run/RunFileTests.cs b/test/dotnet.Tests/CommandTests/Run/RunFileTests.cs
index 5d7b53c65a3e..1a15efebfc71 100644
--- a/test/dotnet.Tests/CommandTests/Run/RunFileTests.cs
+++ b/test/dotnet.Tests/CommandTests/Run/RunFileTests.cs
@@ -3128,7 +3128,13 @@ Release config
         Build(testInstance, BuildLevel.Csc);
     }
 
-    private void Build(TestDirectory testInstance, BuildLevel expectedLevel, ReadOnlySpan<string> args = default, string expectedOutput = "Hello from Program", string programFileName = "Program.cs")
+    private void Build(
+        TestDirectory testInstance,
+        BuildLevel expectedLevel,
+        ReadOnlySpan<string> args = default,
+        string expectedOutput = "Hello from Program",
+        string programFileName = "Program.cs",
+        Func<TestCommand, TestCommand>? customizeCommand = null)
     {
         string prefix = expectedLevel switch
         {
@@ -3138,9 +3144,15 @@ private void Build(TestDirectory testInstance, BuildLevel expectedLevel, ReadOnl
             _ => throw new ArgumentOutOfRangeException(paramName: nameof(expectedLevel)),
         };
 
-        new DotnetCommand(Log, ["run", programFileName, "-bl", .. args])
-            .WithWorkingDirectory(testInstance.Path)
-            .Execute()
+        var command = new DotnetCommand(Log, ["run", programFileName, "-bl", .. args])
+            .WithWorkingDirectory(testInstance.Path);
+
+        if (customizeCommand != null)
+        {
+            command = customizeCommand(command);
+        }
+
+        command.Execute()
             .Should().Pass()
             .And.HaveStdOut(prefix + expectedOutput);
 
@@ -3787,6 +3799,102 @@ public void CscOnly_AfterMSBuild_AuxiliaryFilesNotReused()
         Build(testInstance, BuildLevel.Csc, expectedOutput: "v3 ");
     }
 
+    /// <summary>
+    /// Testing <see cref="CscOnly"/> optimization when the NuGet cache is cleared between builds.
+    /// See <see href="https://github.com/dotnet/sdk/issues/45169"/>.
+    /// </summary>
+    [Fact]
+    public void CscOnly_NuGetCacheCleared()
+    {
+        var testInstance = _testAssetsManager.CreateTestDirectory(baseDirectory: OutOfTreeBaseDirectory);
+
+        var code = """
+            Console.Write("v1");
+            """;
+
+        var programPath = Path.Join(testInstance.Path, "Program.cs");
+        File.WriteAllText(programPath, code);
+
+        var artifactsDir = VirtualProjectBuildingCommand.GetArtifactsPath(programPath);
+        if (Directory.Exists(artifactsDir)) Directory.Delete(artifactsDir, recursive: true);
+
+        var packageDir = Path.Join(testInstance.Path, "packages");
+        TestCommand CustomizeCommand(TestCommand command) => command.WithEnvironmentVariable("NUGET_PACKAGES", packageDir);
+
+        Assert.False(Directory.Exists(packageDir));
+
+        // Ensure the packages exist first.
+        Build(testInstance, BuildLevel.All, expectedOutput: "v1", customizeCommand: CustomizeCommand);
+
+        Assert.True(Directory.Exists(packageDir));
+
+        // Now clear the build outputs (but not packages) to verify CSC is used even from "first run".
+        if (Directory.Exists(artifactsDir)) Directory.Delete(artifactsDir, recursive: true);
+
+        code = code.Replace("v1", "v2");
+        File.WriteAllText(programPath, code);
+
+        Build(testInstance, BuildLevel.Csc, expectedOutput: "v2", customizeCommand: CustomizeCommand);
+
+        code = code.Replace("v2", "v3");
+        File.WriteAllText(programPath, code);
+
+        // Clear NuGet cache.
+        Directory.Delete(packageDir, recursive: true);
+        Assert.False(Directory.Exists(packageDir));
+
+        Build(testInstance, BuildLevel.All, expectedOutput: "v3", customizeCommand: CustomizeCommand);
+
+        Assert.True(Directory.Exists(packageDir));
+    }
+
+    /// <summary>
+    /// Combination of <see cref="CscOnly_NuGetCacheCleared"/> and <see cref="CscOnly_AfterMSBuild"/>.
+    /// </summary>
+    [Fact]
+    public void CscOnly_AfterMSBuild_NuGetCacheCleared()
+    {
+        var testInstance = _testAssetsManager.CreateTestDirectory(baseDirectory: OutOfTreeBaseDirectory);
+
+        var code = """
+            #:property PublishAot=false
+            #:package System.CommandLine@2.0.0-beta4.22272.1
+            new System.CommandLine.RootCommand("v1");
+            Console.WriteLine("v1");
+            """;
+
+        var programPath = Path.Join(testInstance.Path, "Program.cs");
+        File.WriteAllText(programPath, code);
+
+        var artifactsDir = VirtualProjectBuildingCommand.GetArtifactsPath(programPath);
+        if (Directory.Exists(artifactsDir)) Directory.Delete(artifactsDir, recursive: true);
+
+        var packageDir = Path.Join(testInstance.Path, "packages");
+        TestCommand CustomizeCommand(TestCommand command) => command.WithEnvironmentVariable("NUGET_PACKAGES", packageDir);
+
+        Assert.False(Directory.Exists(packageDir));
+
+        Build(testInstance, BuildLevel.All, expectedOutput: "v1", customizeCommand: CustomizeCommand);
+
+        Assert.True(Directory.Exists(packageDir));
+
+        code = code.Replace("v1", "v2");
+        File.WriteAllText(programPath, code);
+
+        Build(testInstance, BuildLevel.Csc, expectedOutput: "v2", customizeCommand: CustomizeCommand);
+
+        code = code.Replace("v2", "v3");
+        File.WriteAllText(programPath, code);
+
+        // Clear NuGet cache.
+        Directory.Delete(packageDir, recursive: true);
+        Assert.False(Directory.Exists(packageDir));
+
+        Build(testInstance, BuildLevel.All, expectedOutput: "v3", customizeCommand: CustomizeCommand);
+
+        Assert.True(Directory.Exists(packageDir));
+    }
+
     private static string ToJson(string s) => JsonSerializer.Serialize(s);
 
     /// <summary>