Trim any excess fat from the brisket, leaving about ¼ inch for moisture. Mix the salt, pepper, garlic powder, onion powder, smoked paprika, and cayenne in a bowl. Rub the brisket generously on all sides and let it sit at room temperature for 30 minutes.
Smoke the Brisket
Preheat your smoker to 225°F using wood like hickory or oak. Place the brisket fat-side up and smoke for about 6 hours, or until it reaches an internal temp of 165°F.
Wrap and Continue Smoking
Wrap the brisket tightly in butcher paper or foil and return it to the smoker. Continue cooking for another 4 hours, until it reaches an internal temp of 200-205°F.
Make the Honey Bourbon Glaze
While the brisket is smoking, combine honey, bourbon, brown sugar, apple cider vinegar, Dijon mustard, Worcestershire sauce, smoked paprika, and chili flakes in a saucepan. Simmer over medium heat for 10 minutes until thickened.
Glaze and Rest
Once the brisket is done, unwrap and brush it generously with the honey bourbon glaze. Let it rest for at least 30 minutes before slicing against the grain.