Perdita Durango (Rosie Perez) has gone to Mexico to scatter the ashes of her dead sister. There, she is picked up by bank-robbing drug dealer Romeo Dolorosa (Javier Bardem). Dolorosa had robbed the bank to pay off his debt to loan shark "Catalina" (Demián Bichir). He also engages in scams in which pretends to be a Santeria priest and hacks up corpses while snorting cocaine.
Romeo's latest scam is working for gangster Mr. Santos (Don Stroud) transporting refrigerated human fetuses to Las Vegas where they will be used to make cosmetic moisturizer.
Perdita devises a plan that they should capture a gringo and eat him as part of Romeo's ceremonies. They kidnap randomly chosen geeky college student Dwayne (Harley Cross) and his girlfriend Estelle (Aimee Graham). First, Perdita rapes Dwayne while Romeo rapes Estelle. They hold a ceremony to sacrifice Estelle while they force Dwayne to watch. Before the girl can be killed the sacrifice is interrupted by a gang of men led by Shorty Dee (Santiago Segura), a betrayed former partner of Romeo.
Romeo and Perdita escape with Dwayne and Estelle still their captives. The four go to the meeting with Santos' people to pick up the truckload of fetuses. Unfortunately, the hand-off is interrupted by drug enforcement agent Woody Dumas (James Gandolfini). Santos' men are all killed. Romeo escapes and drives to Vegas with Dwayne, while Perdita follows with Estelle.
On the trip, Romeo finds out his grandmother's house was raided by some of Catalina's men as punishment for Romeo's unpaid debt. Romeo visits Catalina in a club, pretending to offer Estelle as payment. When he gets Catalina alone, Romeo kills him.
Romeo, Perdita, Dwayne and Estelle finally get to Vegas. However, Dumas has been following them all the way. Moreover, the drop has become a trap for Romeo; Santos is upset about all the deaths at the pick-up so he has hired Romeo's cousin Reggie (Carlos Bardem) to kill Romeo....
Directed by Álex de la Iglesia
Produced by Andrés Vicente Gómez
Written by Barry Gifford
David Trueba
Jorge Guerricaechevarría
Álex de la Iglesia
Starring Rosie Perez
Javier Bardem
Harley Cross
Aimee Graham
Screamin' Jay Hawkins
Don Stroud
Demián Bichir
Santiago Segura
Carlos Bardem
Alex Cox
James Gandolfini
Music by Simon Boswell
Cinematography Flavio Martínez Labiano
Edited by Teresa Font
Rosie Perez as Perdita Durango
Javier Bardem as Romeo Dolorosa
Harley Cross as Dwayne
Aimee Graham as Estelle
James Gandolfini as DEA Agent Willie "Woody" Dumas
Screamin' Jay Hawkins as Adolfo
Demián Bichir as Catalina
Carlos Bardem as Reggie San Pedro
Santiago Segura as Shorty Dee
Harry Porter as Ford
Don Stroud as Santos
Alex Cox as Doyle
Miguel Galván as Doug
César Rodríguez as Dedo Peralta
David Villalpando as Skinny
Josefina Echánove as Romeo's Grandmother
Miguel Iglesias as Danny Mestiza
Katie Barberi as Stewardess
Roger Cudney as Herbert