01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or non-stick spray.
02 - In a large mixing bowl, combine the ground beef, diced onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and pepper. Mix gently with your hands until just incorporated, 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 cooked through.
04 - While the meatloaf bakes, cook the elbow macaroni according to package directions until just al dente. Drain well and set aside.
05 - In a medium saucepan, melt the butter over medium heat. Whisk in the flour and cook for 1 minute to form a roux. Slowly pour in the milk while whisking constantly. Continue cooking and whisking for 2 to 3 minutes until the sauce thickens enough to coat the back of a spoon.
06 - Remove the saucepan from heat. Stir in the shredded cheddar, grated Parmesan, dry mustard, paprika, salt, and pepper. Stir until all the cheese has melted and the sauce is smooth. Fold in the drained macaroni 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 the shredded cheddar, panko breadcrumbs, and melted butter. Sprinkle the mixture evenly across the top of the casserole.
09 - Return the assembled casserole to the oven and bake for 30 to 35 minutes until the top is golden brown and the edges are bubbling.
10 - Remove from the oven and let the casserole rest for 10 minutes before slicing into portions. Serve hot.