Preheat oven to 375 °F (190 °C). Grease a 9×13-inch baking dish.
In a mixing bowl, combine ground beef, breadcrumbs, egg, onion, garlic, ketchup, Worcestershire, Italian seasoning, salt and pepper. Mix gently.
Press the meatloaf mixture into the bottom of the prepared baking dish in an even layer.
Bake the meatloaf base for about 20 minutes.
While meatloaf bakes, cook the macaroni in salted water according to package instructions until al dente. Drain.
In a saucepan, melt butter over medium heat. Whisk in the flour to form a roux, cook for 1 minute.
Slowly whisk in the milk until smooth, and simmer until thickened. Then remove from heat and add the shredded cheddar cheese, stirring until melted. Season with mustard powder and salt.
Stir the cooked macaroni into the cheese sauce, then spread the mac & cheese mixture over the partially baked meatloaf.
Return the casserole to the oven and bake for another 15–20 minutes, until bubbly and golden on top.
Let the casserole rest for 5–10 minutes before slicing and serving.
Notes
You can customize this by using ground turkey, mixing in vegetables like bell peppers, or topping with extra cheese or breadcrumbs before baking.