01 - Preheat the oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or nonstick cooking spray.
02 - In a large mixing bowl, combine the ground beef, chopped onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and pepper. Mix gently with your hands until just combined, being careful not to overwork the meat.
03 - Press the meatloaf mixture evenly into the bottom of the prepared baking dish, creating a uniform layer. Bake for 20 minutes. Remove from the oven and drain any excess fat.
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 over medium heat, melt the butter. Whisk in the flour and cook for 1 minute to form a roux. Slowly pour in the whole milk while whisking constantly. Continue cooking and whisking for 2 to 3 minutes until the sauce thickens slightly.
06 - Remove the sauce from heat and stir in the shredded cheddar, grated Parmesan, dry mustard, smoked paprika, salt, and pepper. Stir until all the cheese is melted and the sauce is smooth. Fold in the cooked macaroni until evenly coated.
07 - Spread the macaroni and cheese mixture evenly over the par-baked meatloaf layer, covering it completely to the edges of the dish.
08 - In a small bowl, combine the shredded cheddar cheese, panko breadcrumbs, and melted butter. Sprinkle the mixture evenly over the top of the casserole.
09 - Return the assembled 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 the casserole from the oven and let it rest for 10 minutes before slicing into portions. Serve hot.