The town of Dillford, Ohio, is home to three species who despise each other: humans, vampires, and zombies. Vampires are the top of the food chain in both literally and in social circles and tend to be the cooler kids in town. The zombies are able to leave their ghetto with special collars that keep them compliant. The humans languish somewhere in the middle, intimidated by the vampires while seeing the zombies as second class citizens. All seem to have their own communities and rules by which they keep a tense truce.
School nerd Dag sets out to lose his virginity with Lorelei, the hottest girl in school to prove he isn’t a loser. He has issues with Rick Wilson, the baseball coach and manager of the local meat factory. Rick fired all of the human employees, including Dag’s mother, and replaced them with zombies as cheap labor. Rick taunts him with this as Dag practices his pitching and he chokes and ends up hitting one of the star athletes, injuring him severely.
Dag’s hippy parents try to cheer him with a speech about the men in his family being late bloomers. When the euphemisms about puberty and “huge changes” make Dag uncomfortable, he stops his well meaning parents and tries to forget about the conversation.
Meanwhile, social outcast Petra is seduced and transformed into a vampire after being bitten by Milan, the high school’s playboy vampire, while they are making out. Later he rejects her when she wants to make the relationship permanent, leaving her alone and now a vampire with no idea how to cope.
Dag’s former best friend Ned, the brother of the athlete Dag injured, is also a social outcast at high school. He is one of the smartest people in the town but is ostracized by his sport loving father and receives only contempt from his teachers. Following an argument with his family, Ned visits the zombie ghetto and he allows a female teenage zombie to bite his leg, transforming him into a zombie so he doesn’t have to think or be smart anymore.
Right as Dag is finally about to score with Lorelei, out of nowhere Aliens invade Dillford, causing residents to believe that the vampires, zombies and humans are attacking each other. This causes an all out war between the three groups that envelopes the town in a free for all of vampires vs. humans vs. zombies.
Dag and Lorelei hide in a house which is raided by a group of vampires and Lorelei is seemingly killed by Petra, who has always been jealous of her. In subsequent brawls between the factions, Dag, Ned, and Petra reluctantly join together and hide in Stuart Miller’s basement, Stuart being the local doomsday nut. While sheltering from the invasion, Petra and Ned are overcome by hunger and eat Stuart and his mother.
The aliens are able to determine their location, causing them to seek cover at the high school. Ned and Dag fight about their former friendship and Dag not wanting to be a loser anymore so they stopped being friends. Ned, who is still a genius despite his non-verbal zombie status, leaves angrily. Later Petra and Dag become trapped and make out, but he flinches and Petra accuses him of being afraid of her. The aliens find them again, and Dag realizes that the aliens can only see inorganic materials, such as their synthetic clothing. The three then strip and run to Dag’s house, where they change into organic cotton clothes kept by Dag’s hippie mother.
Later, Dag, Petra, and Ned are captured by the aliens. They are placed with other captured residents in a warehouse, with force fields segregating the humans, vampires and zombies. Dag and Petra find that instead of dying, Lorelei has been changed into a hot vampire, which intimidates Petra. After figuring out the weakness in the forcefield keeping them apart, Dag, Ned, and Petra convince everyone to band together to fight the aliens and destroy the forcefield..
At Rick Wilson’s meat factory, the chemical “Tetrafluoraxipan” is used to transform horse cartilage into a meat-like substance and is what the aliens are after. Dag convinces Rick to let the town in into the factory as the aliens arrive and submerge in the chemical, combining to grow into a single large alien. It begins to make a speech about how they just wanted to ask nicely for the chemical, but the town’s irritated residents interrupt when it starts getting condescending towards them. The townsfolk attack and the alien fights back but is weakened when the others realize that the ammonia tanks used in the factory can hurt it.
Meanwhile, Milan corners Petra and attempts to kill her. He is stopped by Dag, who turns into a werewolf after almost being killed. He realizes this was the “big change” his parents were trying to talk to him about earlier. After a short brawl, Milan is accidentally killed when he lands on a wooden slab, which impales him.
As the outclassed alien is shrinking back to its mini size, it attempts to escape by spaceship while dropping a bomb to destroy the town. Ned catches the bomb, proving he’s just as good as his athlete brother despite being a zombie. He gives it to Dag who pitches it into the ship before it closes its doors and the spaceship explodes, destroying the alien menace.
Everything returns to normal for the town, and Lorelei asks Dag out on a date. However, Dag chooses to be with Petra instead. Ned appears to be happier and better adjusted as a zombie, and seems to have bonded with his star athlete brother who has also become a zombie.