After a run of bad luck, John (Steve Buscemi), a compulsive gambler, runs away from Las Vegas and into the straight world, taking a nondescript position in an auto insurance company in Albuquerque.
When his boss, Mr. Townsend (Peter Dinklage, The Station Agent ), asks John to accompany his top fraud debunker, Virgil (Romany Malco), on an investigation of a dubious car “accident” near Vegas, John sees an opportunity to get a promotion, though he’s concerned about returning to the gambling game. Before leaving he becomes involved with his eccentric co-worker Jill (Sarah Silverman), a dalliance that has the potential to become a real relationship. Soon John is on the road with Virgil, where they encounter a series of offbeat characters, including a wheelchair-bound stripper (Emmanuelle Chriqui), a nude militant (Tim Blake Nelson), a park Ranger (Jesse Garcia), and a carnival human torch (John Cho). First time writer/director Hue Rhodes’ Saint John of Las Vegas follows the wild and funny trip a guy has to take to discover there’s more than one way to hit the jackpot in life.