故事发生在二十世纪初的墨西哥，四处为非作歹的不法之徒强尼（马克·莱昂纳蒂 Marco Leonardi 饰）带着女友艾丝梅洛达（阿若·希利 Ara Celi 饰）踏上逃亡的旅途，在两人身后紧紧追索的，是艾丝梅洛达身为警察的父亲刽子手（特穆拉·莫里森 uera Morrison 饰）。一行人先后来到了位于茫茫荒漠之中的魔鬼旅店，在那里，一场大战即将拉开序幕。 然而，令众人没有想到的是，打响第一枪的却并非强尼或是刽子手，而是一个性感妖艳的美女。原来，这位美女的真实身份是蛰伏了千年的吸血鬼，再也无法忍受饥渴的她要在此处大开杀戒。艾丝梅洛达竟然主动选择成为吸血鬼的同党，只因为她的体内流淌着一般吸血鬼的血液。"Prequel" to the first From Dusk Till Dawn is set in Mexico in the early 1900's which begins with the escape of Johnny Madrid, a dangerous local outlaw, from the gallows who then kidnaps his hangman's beautiful daughter, Esmeralda, with a little help from Reece, a female outlaw from the U.S. With the hangman and a local posse on their trail, Johnny meets with his gang who all rob a stagecoach which contains American author Ambrose Bierce along with newlywed couple John and Mary Newlie. As night falls, all parties coincidentally seek shelter in an isolated inn/whorehouse which is run by vampires led by the high priestess Quixtla who targets Esmeralda. Esmeralda is revealed to be the half-human, half-vampire princess Santanico Pandemonium, whom the vampires want as their heir in which all the humans must join forces if they are to survive the night from the vicious blood-suckers.
