Jesse and Chester wake up with no recollection of what happened the previous night, except for a few vague memories of partying and consuming copious amounts of alcohol and cannabis. As they try to retrace their steps and locate their car, they encounter a series of bizarre and absurd events.
Their girlfriends, Wilma and Wanda, are furious with them for losing the car, and demand that they find it immediately. However, the duo soon realize that the situation is much more complicated than they initially thought. They meet a group of aggressive street toughs who accuse them of stealing their ostrich, a transvestite stripper who mistakes them for customers, and a group of cult-like aliens searching for a mystical device that could either save or destroy the world.
Jesse and Chester also discover that they have tattoos on their backs, which seem to hold the key to their mysterious night. As the two stoners frantically try to piece together the puzzle, they realize that they inadvertently became embroiled in an intergalactic conflict involving two rival alien factions, each searching for the coveted "continuum transfunctioner".
Despite the chaos and confusion, Jesse and Chester never lose their sense of humor and good nature. Their unwavering friendship and positive attitude allows them to weather the various challenges and obstacles that come their way. Ultimately, they recover their car, foil the alien plot, and come to a newfound appreciation for their bond and the value of life's simple pleasures.