In a bowl, whisk together the buttermilk, 1/2 teaspoon salt, 1/2 teaspoon pepper, and 1 teaspoon cayenne pepper.
Add the chicken thighs to the marinade, turn to coat, cover, and refrigerate for at least 10 minutes or up to 1 hour.
In a separate bowl, combine the flour, 1/2 tablespoon salt, 1 teaspoon pepper, 1 teaspoon garlic powder, and 1 teaspoon onion powder.
Remove a piece of chicken from the marinade, dredge it thoroughly in the seasoned flour, shake off excess, and set aside; repeat with remaining pieces.
Heat 1–2 inches of oil in a deep pot until it reaches 350°F (175°C) or is hot enough that a pinch of flour sizzles on contact.
Carefully fry the coated chicken thighs 7–8 minutes, turning as needed, until golden and cooked through; transfer to paper towels to drain.
Toast the brioche buns if desired, spread mayonnaise on the buns, then layer lettuce, fried chicken, hot honey sauce, and tomato slices; top with the bun lids and serve.