In a small bowl, whisk together the Greek yogurt, mustard, ketchup, and pickle relish to create the secret sauce, then set aside.
Place the ground beef in a bowl and season with garlic powder, onion powder, sea salt, and black pepper, mixing gently with your hands.
Form the beef into a single thick patty, making a slight indentation in the center with your thumb to prevent bulging during cooking.
Heat a non-stick skillet or cast-iron pan over medium-high heat and sear the patty for 4-5 minutes on the first side.
Flip the patty and immediately place the cheddar cheese slice on top, covering the pan with a lid for the final 3-4 minutes to melt the cheese.
While the beef rests for 2 minutes, lightly toast the whole wheat bun in the same pan or a toaster until golden.
Spread the secret sauce on both sides of the bun, then layer the lettuce, tomato, and onion on the bottom half.
Place the cheeseburger patty on top of the vegetables, close the bun, and serve immediately.