Mix together chili powder, cumin, garlic powder, cayenne pepper, salt, and ground black pepper in a small bowl.
Heat a large skillet over medium-high heat and cook ground beef, stirring often, until the meat is crumbly, evenly browned, and no longer pink, about 10 minutes. Mix in onion and garlic; cook and stir until the onion has softened and turned translucent, about 5 minutes. Stir spice mixture into ground beef mixture and cook until fragrant, 2 to 3 more minutes.
Combine salsa, sour cream, and lime juice in a small bowl. To serve, spread shredded romaine lettuce onto a serving platter and top with meat mixture, salsa mixture, cherry tomatoes, Cheddar cheese, and chopped cilantro.