In a large bowl, combine the ground beef, breadcrumbs, milk, beaten egg, ketchup, Worcestershire sauce, garlic powder, onion powder, salt, and pepper. Mix gently until well combined.
Divide the meat mixture into 4 equal portions and shape each portion into a patty about the same size as your sandwich bread.
Preheat a large skillet or grill pan over medium-high heat. Add the meatloaf patties and cook for 6-8 minutes on each side or until they reach an internal temperature of 160°F. Remove the patties from the heat and let them rest for 5 minutes.
Toast the sandwich bread slices until lightly golden brown, spread mayonnaise on one side of each toasted bread slice.
Place a lettuce leaf on the bottom slice of bread, followed by a meatloaf patty, a slice of red onion, and a tomato slice. Top with the remaining toasted bread slice, mayonnaise side down. Repeat the assembly process for the remaining sandwiches.
Serve the sandwiches immediately while the patties are still warm, enjoy!