"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 coincidently 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.

In this sequel to 'Desperado', a Mexican drug lord pretends to overthrow the Mexican government, and is connected to a corrupt CIA agent who at that time, demands retribution from his worst enemy to carry out the drug lord's uprising against the government.

A famous film director remembers his childhood at the Cinema Paradiso where Alfredo, the projectionist, first brought about his love of films. He returns home to his Sicilian village for the first time after almost 30 years and is reminded of his first love, Elena, who disappeared from his life before he left for Rome.