The novel focuses on Scott Crane, a professional gambler and grieving middle-aged widower who is the son of Georges Leon, a powerful occultist and mobster.

Leon also uses a system of Tarot card sorcery to transfer his consciousness into other people's bodies in an attempt to attain immortality, at the cost of turning the person into a mindless automaton.

Like many of Powers' novels, Last Call features a detailed magic system, here based on divinatory tarot, and draws on mythical or historical events and characters.

Powers uses details of real-life mobster Bugsy Siegel life, and the development of Las Vegas casinos as well as the legend of the Fisher King.

Powers' self-imposed rules prohibit him from disregarding established historical facts and timelines, instead finding alternate supernatural explanations for real-world events which he incorporates into his fiction, a genre known as a "secret history".