Preheat Oven: Heat the oven to 350°F (175°C). Grease a 9×13-inch baking dish generously.
Prepare Meatloaf: In a large mixing bowl, combine the ground beef, eggs, onion soup mix, crushed crackers, onion powder, garlic powder, salt, and pepper. Add half of the ketchup-BBQ sauce mixture and knead with your hands until well combined.
Bake Meatloaf: Press the meatloaf mixture into the prepared baking dish. Spread the remaining ketchup-BBQ sauce mixture on top and bake for 30 minutes.
Cook Macaroni: While the meatloaf is baking, cook the macaroni noodles until al dente, then drain.
Prepare Cheese Sauce: In a saucepan, combine the milk, cheddar cheese soup, onion powder, garlic powder, salt, and pepper. Stir over medium heat until smooth. Add 1 cup each of mozzarella and cheddar cheese, stirring until melted. Toss in the cooked macaroni.
Layer Macaroni Over Meatloaf: Once the meatloaf has baked, spread the macaroni mixture over the meatloaf. Top with the remaining shredded cheese.
Bake Again: Return the casserole to the oven and bake for an additional 20 minutes, or until the cheese is bubbly and melted.
Rest and Serve: Allow the casserole to rest for 5-10 minutes before serving.