Preheat the oven to 350°F (175°C).
In a large bowl, combine the ground beef, bread crumbs, salsa, shredded cheese, cilantro, red onion, egg, chili powder, cumin, paprika, garlic powder, salt, and black pepper. Mix until well combined.
Transfer the mixture to a greased loaf pan and press it down evenly.
In a small bowl, whisk together the ketchup, brown sugar, and Worcestershire sauce. Spread the mixture over the meatloaf.
Bake in the preheated oven for 1 hour, or until the internal temperature reaches 160°F (71°C).
Remove from the oven and let rest for 5 minutes before slicing.
Serve the Mexican Meatloaf with additional salsa, if desired.
Enjoy!