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Gather the ingredients.
Preheat the oven to 400 F/200 C and lightly grease a large shallow baking pan—such as a jelly roll pan —or spray with nonstick cooking spray.
Combine the mayonnaise and mustard in a small bowl; rub the mixture over the tilapia fillets.
Combine the panko and fine bread crumbs, parsley, paprika, onion powder, salt, and pepper in a food processor . Pulse 4 to 6 times to combine.
Pour bread crumbs mixture into a wide, shallow bowl. Dip the coated fillets in the mixture, turning to coat both sides.
Arrange the coated fillets in the prepared baking dish.
Bake the fish fillets for 15 to 20 minutes or until fish is cooked through, depending on the thickness of the fillets. Fish will flake easily with a fork when done.
Carefully remove the tilapia fillets to plates with a spatula.