Guilty Pleasures introduces the character of Anita Blake, Vampire Hunter and her world, an alternate history where magic, vampires, werewolves and other supernatural elements are known to exist. Blake, a zombie animator and licensed vampire executioner, is forced to investigate a series of vampire murders, and in the process comes into contact with many of the supernatural characters of her home city of Saint Louis. The novel blends elements of supernatural and hardboiled detective fiction.

Within the novel, "Guilty Pleasures" is the name of a vampire strip club operated by Jean-Claude, one of the main characters. Hamilton has continued the pattern of titling the novels after a location within each novel for most of the books in the series.