Bloody Bones continues the adventures of Anita Blake. This time, Anita travels to Branson, Missouri and is quickly enmeshed in a series of supernatural murders and disappearances that she and her vampire would-be lover, Jean-Claude must resolve. As with its predecessors, Bloody Bones blends elements of supernatural, hardboiled and police procedural fiction.

Within the novel, "Bloody Bones" is the name of a restaurant that is operated by two of the principal characters in the novel, Magnus and Dorcas Bouvier. Hamilton employed the practice of naming each novel after a fictional location within the story for most of the Anita Blake series. In this case, the restaurant itself is named after a character in the novel, Rawhead and Bloody Bones, making the title somewhat eponymous.