01 - Preheat oven to 350°F. Lightly grease a 9x13-inch baking dish with butter or nonstick spray.
02 - In a large mixing bowl, combine ground beef, diced onion, minced garlic, breadcrumbs, egg, milk, ketchup, Worcestershire sauce, salt, and pepper. Mix gently with your hands until just combined—avoid overworking the mixture to keep it tender.
03 - Press the meat mixture evenly into the bottom of the prepared baking dish, creating a uniform layer. Bake for 20 minutes. Carefully drain off any excess grease from the pan.
04 - While the meatloaf bakes, cook 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 enough to coat the back of a spoon.
06 - Remove the saucepan from heat. Stir in the shredded cheddar, grated Parmesan, dry mustard, smoked paprika, salt, and pepper. Stir until the cheeses are completely 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, pressing gently to create a level surface.
08 - In a small bowl, combine shredded cheddar, panko breadcrumbs, and melted butter. Mix until the breadcrumbs are evenly moistened. Sprinkle the topping uniformly over the casserole.
09 - Return the casserole to the oven and bake for 30 to 35 minutes until the top is deeply golden and bubbling around the edges. The internal temperature of the meatloaf layer should reach 160°F.
10 - Remove from the oven and let rest for 10 minutes before slicing into portions. Serve hot.