The title character of this Alex de la Iglesia film made her first appearance in David Lynch's Wild at Heart (1990) and was originally played by Isabella Rossellini. Rosie Perez takes over the role in this blend of black comedy, graphic sex and violence, voodoo, and weirdness. Perdita Durango is pure trash, a fact she establishes at the film's beginning.
Her adventures begin when she hooks up with Romeo Dolorosa (Javier Bardem), a sleek, black-clad, sexually adventurous practitioner of Santeria who routinely kills, robs banks, and steals corpses from graves for his cannibalistic blood-soaked rituals. Santos (Don Stroud) is a pedophile and a crime boss.
He hires Romeo to steal a truck filled with human fetuses that are slated to be used for cosmetic experiments. Romeo accepts but feels he must make a human sacrifice before he goes. This bothers Perdita not a bit and she even picks out a pair of blonde teens for the ritual killing.
The two crooks kidnap the kids, ritually feather them, sexually abuse them, and are preparing to kill them when Romeo's cheated partner shows up with policemen. The crooks and their prey manage to escape, but the scheme to commandeer the truck gets botched and an ensuing shootout between Santos' men and DEA agents goes wrong.
Santos loses many men and swears revenge upon Romeo and Perdita, who continue on their journey with their two doomed victims.