In a large bowl, combine the chicken tenders, buttermilk, and hot sauce if using. Toss to coat. Cover and refrigerate for at least 1 hour (or overnight for best results).
In another bowl, whisk together the flour, paprika, garlic powder, onion powder, cayenne pepper, salt, and pepper.
Remove the chicken from the marinade, letting the excess drip off. Dredge each piece in the seasoned flour, pressing lightly so the coating sticks well.
Heat about 1–2 inches of vegetable oil in a deep skillet over medium heat to 350°F (175°C). Fry the chicken in batches, about 3–4 minutes per side, until golden brown and cooked through.
Transfer the cooked tenders to a paper towel-lined plate to drain. Serve hot with your favorite dipping sauces.