diff --git a/src/Files.App.CsWin32/NativeMethods.txt b/src/Files.App.CsWin32/NativeMethods.txt
index 9f10fdd3870b..9d900f53d0e9 100644
--- a/src/Files.App.CsWin32/NativeMethods.txt
+++ b/src/Files.App.CsWin32/NativeMethods.txt
@@ -267,3 +267,4 @@ WINTRUST_DATA
 HCERTSTORE
 CERT_QUERY_ENCODING_TYPE
 CertGetNameString
+MessageBox
diff --git a/src/Files.App/Constants.cs b/src/Files.App/Constants.cs
index c3a531e502dd..578c8951644f 100644
--- a/src/Files.App/Constants.cs
+++ b/src/Files.App/Constants.cs
@@ -282,5 +282,13 @@ public static class Distributions
 				"FilesDev", // dev
 			};
 		}
+
+		public static class Startup
+		{
+			// These strings are intentionally hardcoded and cannot be moved to resource files.
+			// The Windows App Runtime (which powers the resource loading system) may itself be unavailable at this point
+			public const string MissingRuntimeMessage = "Files failed to start. A required Windows component could not be loaded. Try reinstalling Files from the Microsoft Store or from https://files.community/download";
+			public const string MissingRuntimeTitle = "Files - Startup Error";
+		}
 	}
 }
diff --git a/src/Files.App/Program.cs b/src/Files.App/Program.cs
index 5676b750ed43..91702da505af 100644
--- a/src/Files.App/Program.cs
+++ b/src/Files.App/Program.cs
@@ -6,7 +6,9 @@
 using Microsoft.UI.Xaml;
 using Microsoft.Windows.AppLifecycle;
 using System.IO;
+using System.Runtime.InteropServices;
 using System.Text;
+using Windows.Win32.UI.WindowsAndMessaging;
 using Windows.ApplicationModel.Activation;
 using Windows.Storage;
 
@@ -101,7 +103,23 @@ static bool ProcessPathPredicate(Process p)
 			//Server.AppInstanceMonitor.StartMonitor(Environment.ProcessId);
 
 			var OpenTabInExistingInstance = ApplicationData.Current.LocalSettings.Values.Get("OpenTabInExistingInstance", true);
-			var activatedArgs = AppInstance.GetCurrent().GetActivatedEventArgs();
+
+			AppActivationArguments activatedArgs;
+			try
+			{
+				activatedArgs = AppInstance.GetCurrent().GetActivatedEventArgs();
+			}
+			catch (COMException ex) when (ex.HResult == unchecked((int)0x80040154))
+			{
+				Windows.Win32.PInvoke.MessageBox(
+					default,
+					Constants.Startup.MissingRuntimeMessage,
+					Constants.Startup.MissingRuntimeTitle,
+					MESSAGEBOX_STYLE.MB_ICONERROR);
+
+				throw new InvalidOperationException(Constants.Startup.MissingRuntimeMessage, ex);
+			}
+
 			var commandLineArgs = GetCommandLineArgs(activatedArgs);
 
 			if (commandLineArgs is not null)