Inspired by a comic book given to him by White Wolf business partner Stewart Wieck, Rein-Hagen developed the idea that the cursed character of the Biblical Cain was the original vampire. Some of Vampire 's central themes of the power of belief developed out of Rein-Hagen's religious upbringing. He wanted to go beyond what Anne Rice had done by creating individual vampires, with a whole secret vampire society and culture. Rein-Hagen stated that he purposefully did not read Anne Rice's Vampire Chronicles until 'very late' in the development process but admitted she was probably an influence on the vampire films that inspired the game. Rein-Hagen felt that hunting vampires, as a game premise, would get boring, so he came up with the idea of a game wherein the players played vampires instead of hunting them.

Vampire was inspired by role-playing games (RPGs) such as Call of Cthulhu, RuneQuest, and Nightlife, as well as the writings of Joseph Campbell and vampire films such as The Lost Boys.

In 1996, a short-lived television show loosely based on the game, Kindred: The Embraced, was produced by Aaron Spelling for the Fox Broadcasting Company. Several associated products were produced based on Vampire: The Masquerade, including live-action role-playing games ( Mind's Eye Theatre), dice, collectible card games ( The Eternal Struggle), video games ( Redemption, Bloodlines, Swansong and Bloodlines 2, Bloodhunt), and numerous novels.

It is set in a fictionalized 'gothic-punk' version of the modern world where players assume the role of vampires, who are referred to as 'Kindred.' and deal with their night-to-night struggles against their own bestial natures, vampire hunters, and each other. Vampire: The Masquerade is a tabletop role-playing game (tabletop RPG) created by Mark Rein-Hagen and released in 1991 by White Wolf Publishing as the first of several Storyteller System games for its World of Darkness setting line.

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