No problems beyond the obvious, e.g., there is no backing up. However, be sure that your state allows it as many don't.
Some states that do allow you to tow a trailer behind a 5th Wheeler have different overall length requirements for 5th Wheel RVs than commercial tractor-trailer rigs and there may be additional restrictions. As an example, Minnesota law says:
169.81 Subd. 3c.Recreational vehicle combination.
Notwithstanding subdivision 3, a recreational vehicle combination may be operated without a permit if:
(1) the combination does not consist of more than three vehicles, and the towing rating of the full-size pickup truck or recreational truck-tractor is equal to or greater than the total weight of all vehicles being towed;
(2) the combination does not exceed 70 feet in length;
(3) the operator of the combination is at least 18 years of age;
(4) the trailer is only carrying watercraft, motorcycles, motorized bicycles, off-highway motorcycles, snowmobiles, all-terrain vehicles, motorized golf carts, or equestrian equipment or supplies, and meets all requirements of law;
(5) the vehicles in the combination are connected to the full-size pickup truck or recreational truck-tractor and each other in conformity with section 169.82; and
(6) the combination is not operated within the seven-county metropolitan area, as defined in section 473.121, subdivision 2, during the hours of 6:00 a.m. to 9:00 a.m. and 4:00 p.m. to 7:00 p.m. on Mondays through Fridays.