Heat a skillet over medium heat and add ground beef and diced onion. Break apart the meat and season with salt, black pepper, paprika, Italian seasoning, onion powder, and crushed red pepper flakes. Cook for about 6 to 8 minutes until the beef is no longer pink.

Add chopped pepperoni to the skillet and mix. Drain excess grease and stir in marinara sauce and minced garlic until well combined.

In a separate bowl, whisk together Bisquick mix, milk, and eggs until smooth and slightly fluffy. Set aside.

Spray a pie pan with non-stick cooking spray. Layer half of the beef mixture, then a cup of shredded mozzarella cheese. Repeat with remaining beef mixture and another cup of cheese.

Pour the Bisquick batter over the assembled filling, letting it settle into gaps.

Sprinkle extra chopped pepperoni on top and bake in a preheated oven at 400°F for approximately 25 minutes until the top is golden brown.

Let the pie rest for a few minutes before slicing, then serve warm.