Preheat a smoker to 250°F. Set it up for indirect cooking.
In a small bowl, mix the softened cream cheese, pepper jack, and diced jalapeño until combined. Set the filling aside.
In a large bowl, combine the ground beef, panko, egg, milk, onion, garlic powder, smoked paprika, salt, and black pepper. Mix gently just until everything is evenly distributed.
Place the meat mixture on a sheet of parchment and shape it into a rectangle about 1 inch thick. Spread the cheese mixture down the center, leaving a border around the edges. Use the parchment to fold the meat over the filling, then pinch the seams and ends closed. Shape into a loaf with the seam underneath.
Transfer the loaf to a smoker-safe pan or a piece of foil. Smoke until the center reaches 150°F, about 1 1/2 to 2 hours depending on its shape and the smoker.
Brush the top and sides with half of the BBQ sauce. Continue smoking until the center reaches 160°F, then brush with the remaining BBQ sauce. Rest the meatloaf for 10 minutes before slicing so the filling can settle.