01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or non-stick spray.
02 - In a large bowl, combine ground beef, chopped onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and black pepper. Mix gently until just combined, being careful not to overwork the meat.
03 - Press the meat mixture evenly into the bottom of the prepared baking dish, creating a uniform layer. Bake for 20 minutes until partially set.
04 - While the meatloaf bakes, cook elbow macaroni according to package instructions until just al dente. Drain thoroughly 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 whole milk while whisking constantly. Continue cooking and stirring for 2 to 3 minutes until the sauce thickens slightly.
06 - Stir shredded cheddar, grated Parmesan, dry mustard, paprika, salt, and pepper into the sauce. Stir until all cheese has melted and the sauce is smooth. Fold in the drained macaroni and mix until evenly coated.
07 - Spread the macaroni and cheese mixture evenly over the partially baked meatloaf layer, covering it completely to the edges.
08 - In a small bowl, combine shredded cheddar cheese, panko breadcrumbs, and melted butter. Sprinkle this mixture evenly across the top of the casserole.
09 - Return the casserole to the oven and bake for 30 to 35 minutes until the topping is golden brown and the casserole is bubbling throughout.
10 - Remove from the oven and let rest for 10 minutes before slicing into portions. Serve hot.