Slasher College Roadtrip V is the 2004 sequel to the 2002 horror film Slasher College IV: Blood Lake, and the fifth in the entire franchise. The story revolves around the two surviving protagonists from previous films: Lisa (the survivor of the the murders of her friends in Texas, the return of the killer at Massachussetts University and the incident at Blue Lake camp) and Amber Truscott, the survivor of the murders at the Terror Train 3D amusement park. Both girls have been admitted to the same mental asylum, and escape after the killer, named finally as Bullethead attacks the asylum. It is the last Slasher College Roadtrip film to be directed by Rob MacNamara until 2009's prequel Slasher College Roadtrip VIX: Resurrection.
Shortly after escaping the killer at Blue Lake, Lisa is admitted to a local mental asylum, the same as Amber Truscott, the survivor of the murders at the Terror Train 3D amusment park. During their admittance they become friends as they believe each other's story. Another who believes is Investigator Ben Lanley, who agrees to help the girls find the killer. After Ben leaves he heads the the car park of the metal asylum where the rest of his team are, to find them all brutally killed. He tries run back into the asylum, fearing that the killer has already struck, but finds the doors closed behind. As he struggles the get in the killer stalks through the asylum hallways, killing workers but leaving the patients unharmed. Ben finally breaks in through the window as the killer approaches Amber and Lisa's rooms, and shoots him with a shotgun. The shot maims the killer, but he continues ahead, ignoring Ben. He calls back "Bullethead!" after noticing the bulletholes in the killer's head, provoking him. The killer then turns around and swings his machete in a circular notion as he approaches Ben. He tries to step back but trips, where the killer almost gets him before Amber knocks him out with a fire hydrant. Ben gets up, and notices the mess the killer has caused, rushes the two into his car and drives them to the police station. Meanwhile the killer is resuscitated and stands, growling.
Meanwhile a bunch of stoner college students (Micky, Joanna, Les, Paulie, and Raph), inadvertantly linked to the others by being from Massachussetts College, attract the attention of the killer after he recognises their unforms. He proceeds to murder them one by one rather messily (decapitates Micky and Joanna, impales Les, strangles Paulie and disembowels Raph). He then leaves, on the scent of Ben's car, heading to the police station. As they arrive at the station, Ben receives a phone call from the chief of police, Bob Berkley, who is in the centre of town trying to combat the killer. Ben rushes Lisa and Amber inside, getting back into his car and heading to the scene. As he drives off they notice Bullethead in the back of his car, grabbing Ben by the neck. The car crashes, and they witness Bullethead dragging Ben from the wreckage and stabbing him in the leg, before carrying him off. He is taken to the killer's lair, an underground bunker with various trophies, including newspaper headlines detailing his previous murders in the past films. Ben is strapped to a chair, and his teeth removed by Bullethead slowly with a pair of pliers. He retches in disgust, and his captor stabs him in the knee as punishment. Back at the police station Lisa and Amber are in police custody, and Chief Bob Berkley is asking them about the killer and how he was defeated earlier. Suddenly the station is alerted and everyone rushes out to see the silhouette of what appears to be Ben. Berkley calls out, before Ben falls in half and Bullethead steps forward. Berkley shouts at the killer for murdering Ben, and begins shooting him along with the other policemen. Amber and Lisa escape as Bullethead massacres the police, electrocuting Berkley in a final confrontation.
Shocked by the brutal death of Ben, Lisa is hesitant to head into the woods with Amber in a bid to escape; recalling the incident at Blue Lake camp. When they see Bullethead in pursuit they run into the woods and find an abandoned RV, which they hijack and flee in. Bullethead, possessing immense agility and strength, chases the RV and launches himself onto the roof. He uses his trademark machete to stab a hole in the roof and climbs into the RV. As Amber frantically steers the car Lisa confronts Bullethead with various utensils in the RV, stabbing him several times and distracting him enough to give her the chance to kick him out the back door. As she closes the door Lisa turns to Amber, before she unwittingly crashes the RV into a tree. Lisa screams, and after the car stops moving she goes to the driver's seat; where Amber's face has been crushed by the impact. She screams again and flees the RV, with a dazed Bullethead pursuing her. After she is trapped by the killer she struggles and manages to push him off a cliff to his death. As she staggers back to town she sobs, her hands stained with blood.