New guns and gun upgrades can be bought with cash earned from the player's end of level score, between levels at the Gun Shop. Upon completing the story mode, Director's Cut is unlocked providing the same game as story mode but with tougher enemies, extended levels and a limited amount of continues.
Plot
Years ago during the Cold War, the U.S. military made a new superhuman formula called Formula X but the project for its use failed. The bunker for the experiments was shut down and abandoned. In 1991, seven years before The Curien Mansion Incident, AMS Special Agent G is given his first assignment and sent to a small town in Louisiana to investigate a series of disappearances and hunt down a deranged crime boss, Papa Caesar. Due to the presence of mutants, G is forced to team up with police detective Isaac Washington who is out to avenge his father's murder, which Caesar masterminded.
In the first episode "Papa's Palace of Pain", the pair first storm a mansion owned by Caesar out in the woods. Upon entering the basement, they find Caesar has fled, and the disabled scientist Jasper Guns, whom Caesar used, is horrifically mutated from injecting himself with an unknown substance. Upon defeating Jasper, G and Isaac meet Varla Guns, a stripper and Jasper's older sister who vows revenge on Caesar. In the second episode, "Ballistic Trauma", G and Isaac track Caesar to a hospital that is swarming with mutants. After killing the mutants and a mutant woman called the Screamer, they find a ringing phone hidden inside it. Caesar answers from the other end and the hospital is set to explode. G and Isaac escape in the nick of time with Varla on a motorbike. In the third episode, "Carny", they stop at a mutant infested carnival to investigate the mutant situation, in the process defeating former circus entertainers turned horrific creature Nigel & Sebastian. Afterwards, they continue to follow Caesar on an ice cream truck. In the fourth episode, "Scream Train", they and Varla catch Caesar at a train station. But they argue over what to do with him: G wants to arrest him, Issac wants to avenge his father, and Varla wants to avenge her brother. Caesar then escapes on a train with G and Isaac giving chase while Varla is left behind. The pair made their way through the mutant-infested train, defeating a mutated mantis, the Crawler, in the process. An explosion causes the train to crash in a swamp where Caesar takes Varla hostage and drives off before throwing a cassette tape to Isaac. In the fifth episode, "Fetid Waters", G and Isaac make their way to the swamps, finding an alternate way to wherever Caesar and Varla were heading for, and in the process, defeat another boss mutant called the Lobber.
In the sixth, penultimate episode 'Jailhouse Judgment', G and Isaac track Caesar to a high security prison. Before they enter, they run into its strange warden, Clement Darling, who noticed where Caesar and Varla headed but knows nothing about the mutants. As G and Isaac shoot their way through the prison they finally reach the electric chair theater where Varla and Caesar are strapped into the chairs. Clement then appears and, in a plot twist, reveals that he was behind the mutant outbreak and that Caesar was just an accomplice. Clement then executes Caesar, robbing Isaac of his revenge. Clement explains that his experiments were to save his dying mother (following this, it is implied Clement has an incestuous relationship with his mother). Clement then descends on a giant elevator along with Varla, his mother, and Caesar's corpse. Seconds later, Clement tells G and Isaac to look at the stage behind them where two gigantic, physically enhanced, convicts wearing black masks lumber in through the door. Clement reads the two convicts' previous crimes which include murder, assault, rape, and even eating a little boy's puppy. One of the convicts, Brutus, suddenly turns around and beats his fellow convict to death before turning his attention to G and Isaac.
After killing Brutus and descending the elevator in pursuit of Clement in the final episode "Overkill", G and Isaac shoot their way through hordes of mutants inside Clement's underground lab before finally reaching his center of operations. They discover Varla's brain has been taken out, kept alive in a jar, while Clement's mother's brain has been transplanted into Varla's body. At first it seems the experiment was a success, then Varla's body begins to vomit and she falls into a pit after being gunned down by G and Isaac, mutating her into a giant monster. G and Isaac draw their guns and aim them at the newly mutated Mother. The duo's statements lead gamers to believe that they are about to play a frantic last stand shootout against the giant mutant, but then the screen cuts to a missing reel screen for a few moments. Once the reel resumes G and Isaac are outside claiming victory over Clement and the giant monster, thanking the use of miniguns they found randomly lying around nearby. However, the monster returns and the pair battle her again. After finally killing it, Clement appears and seeks to atone for all the problems he caused by "returning to the womb" and enters the monster's body.
G and Isaac are picked up by a helicopter along with Varla's (still active) brain in a jar where Isaac releases the detonator to destroy the facility. G tells Varla of his feelings for her, prompting him and Isaac to discuss the moral and political messages in the game's storyline and potential backlash, particularly from feminists. Soon after, the two realize the helicopter is being piloted by a mutant and point their guns at it, ending the game.
In Extended Cut, there are two new levels featuring Varla Guns and a stripper named Candi Stryper, who was in love with Jasper Guns. It is a side story during the main game (set after the second and fourth levels). It sees the girls traveling through a strip club and a meat packing plant, fighting grotesque mutant strippers Coco and Sindy, as well as Meat Katie, a minotaur-like female butcher. The side story ends with Candi dying of blood loss after the battle with Meat Katie.
After the credits roll, Caesar's tape recording from before is played, revealing a message to Isaac that Clement's plans were small-minded but he has powerful friends (possibly the future DBR corporation), and that Isaac's father is still alive.