01 - Preheat the oven to 350°F. Lightly grease a 9×13-inch baking dish with butter or nonstick spray.
02 - In a large mixing bowl, combine the ground beef, finely chopped onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and black pepper. Mix gently until just incorporated—avoid overworking the meat to keep it tender.
03 - Press the meat mixture evenly into the bottom of the prepared baking dish. Bake for 20 minutes to partially cook 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 whole milk while whisking constantly, and continue cooking for 2 to 3 minutes until the sauce slightly thickens.
06 - Stir the shredded cheddar, grated Parmesan, dry mustard, paprika, salt, and pepper into the sauce until the cheeses are fully melted and smooth. Fold in the cooked macaroni until evenly coated.
07 - Spread the macaroni and cheese mixture evenly over the partially baked meatloaf layer in 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 casserole to the oven and bake for 30 to 35 minutes until the top is golden brown and bubbling throughout.
10 - Remove from the oven and let the casserole rest for 10 minutes before slicing. Serve hot.