01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or nonstick spray.
02 - In a large bowl, combine ground beef, onion, garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and pepper. Mix gently until just combined without overworking the meat.
03 - Press the meat mixture evenly into the bottom of the prepared baking dish. Bake for 20 minutes until partially cooked through.
04 - While the meatloaf bakes, cook elbow macaroni according to package instructions until just al dente. Drain well and set aside.
05 - In a medium saucepan, melt butter over medium heat. Whisk in flour and cook for 1 minute to form a roux. Slowly pour in milk while whisking constantly and cook for 2-3 minutes until slightly thickened.
06 - Stir cheddar and Parmesan cheeses, dry mustard, paprika, salt, and pepper into the sauce until melted and smooth. Fold in the cooked macaroni and mix until evenly coated.
07 - Spread the macaroni and cheese mixture evenly over the partially baked meatloaf layer in the baking dish.
08 - In a small bowl, combine shredded cheddar cheese, panko breadcrumbs, and melted butter. Sprinkle the mixture evenly over the casserole surface.
09 - Return the casserole to the oven and bake for 30-35 minutes until the top is golden brown and bubbling. Remove from oven and let rest for 10 minutes before slicing. Serve hot.