Lisa: The Painful

Both The Painful and The Joyful take place in a post-apocalyptic wasteland called Olathe. Once a normal town, following an unseen cataclysm known as "The Flash", all women have perished, and humanity was left with no way to reproduce. Many have resorted to Joy, a highly addictive drug spread by a gang leader named Buzzo, that makes people "feel nothing", in order to numb the pain. However, unbeknownst to its users, it eventually causes them to become deformed, mindless creatures known as Joy Mutants. The strongest group in the wasteland is the army of Rando, a powerful martial artist and warlord who always wears a skull-shaped mask.

The game starts during a flashback, in which the player controls a child named Bradley Armstrong. The departure of his mother leads to Bradley and his younger sister, Lisa, to be abused and neglected by their father, Marty Armstrong. The game then skips forward to the post-apocalyptic future, where Brad, now a middle-aged ex-martial arts instructor, lives with his friends. One day, he discovers a baby girl laying in the wasteland. While his friends plead for him to give the child to Rando, Brad refuses, instead raising the young girl he christens "Buddy" in secret. She is eventually found and seemingly kidnapped, leading Brad to embark on a journey across Olathe to rescue her.

During his quest, Brad meets many different characters, some of whom may be recruited as party members by the player to be used in combat. Throughout the game, flashback scenes depict a pre-apocalyptic Olathe, shedding light on Brad's early life, including his upbringing alongside his younger sister Lisa and their relationship with Marty. Brad also repeatedly encounters Buzzo, who forces him to make serious choices with permanent gameplay consequences.

Brad and Buddy are later reunited, and Brad realizes that Buddy left on her own due to Brad's controlling nature. Brad still decides to take Buddy back to their home, but he is cornered by Buzzo and his gang, who knock him out and force-feed him Joy in front of his daughter. Brad has a Joy-induced blackout, and when he wakes up he finds that Buzzo, his group, and Buddy are gone. Despite realizing Buddy's distaste towards him, Brad pushes forwards, his past trauma causing him to desperately fear that harm will befall Buddy. After hearing that Buddy stole a boat and presumably went out to sea, Brad makes one of his own, and while his party members are asleep, sets off alone. He finds Buddy on a desolate island, being cared for by an aged Marty, whom Brad promptly kills in a Joy-fueled rage. When Buddy escapes yet again, he uses a corpse as a flotation device to follow her.

When he reaches land, Brad encounters Rando, who found Buddy and took her under his care. Unexpectedly, Brad's party members arrive, and try to convince him to let Rando take care of Buddy. Brad, obsessed with reuniting with his adoptive daughter, and taking this as a threat, kills his own party members. Despite the odds, Brad massacres Rando's forces, and then, apparently, Rando himself. Brad finally reaches Buddy, and she blames him for ruining her chances at freedom alongside Rando. The game then shifts perspective to Buddy. As Brad dies, he asks if he did the right thing, and the player chooses whether or not Buddy hugs him in response, though this has no impact on the story. Brad then falls over, apparently dead. After the credits, it is revealed that Brad has transformed into a Joy Mutant. The ending the player receives depends on whether they elected to play on Pain Mode or use the drug Joy.

The game's DLC chapter takes place immediately after the end of the second game. It is revealed that Rando was not killed in his battle with Brad. He accompanies Buddy as she tries to become the most powerful person in Olathe by killing the warlords ruling it, despite Rando's disapproval. Following the kidnapping of Buddy by associates of Rando alongside Buddy's slaughter of a village inhabited by pacifists, Rando leaves Buddy, presumably due to his distaste for the senselessness of the violence she seeks to unleash upon Olathe. Rando is subsequently captured by a man by the name of Bolo Bugaughtiichi, who utilizes him as bait in an ultimately unsuccessful effort to capture, and rape, Buddy. Regardless of player choice, Bolo is unsuccessful, and is killed: either by Buddy or by a mutated creature nicknamed "Sweetheart". After Rando is horribly injured in the fall from the trap, he reveals that he was behind the kidnapping in an attempt to keep Buddy safe and protected. Buddy, in a violent rage, kills Rando. Afterwards, Buddy suffers from various hallucinations, implied to be the byproduct of taking Joy, such as seeing Brad and Rando.

After defeating all of the game's warlords, Buddy confronts Dr. Yado, a trumpet-playing professor who appears in secret locations in The Painful, but cannot be interacted with. Yado, a mad scientist who created Joy, and likely caused the Flash, used Buzzo to spread Joy throughout Olathe in an attempt to destroy civilization and rule the world. The last part of his plan is to murder Buddy, the one force strong enough to bring him down. Buddy is suddenly ambushed by Sweetheart, but is saved by Buzzo, who informs her that Yado has a vaccine that can prevent her from becoming a Joy Mutant. After Yado's defeat, he begins to verbally confront Buddy, revealing himself to be her biological father, and asserts that he has control over her. He is suddenly killed by a horribly injured Buzzo, who renounced both of their evil actions.

Buzzo explains that he was formerly Lisa's lover, and blamed Brad for failing to prevent his father's abuse, which eventually led to Lisa's suicide. This is what made him torment Brad throughout The Painful. After insisting that Brad was Buddy's true father and a good man, he mutates due to his own secret Joy use, and commits suicide via biting off his own neck. The player then has to make a final choice. Buddy is due to mutate regardless of the player's Joy use. Buddy can choose to take or refuse the vaccine, which stops Joy's mutagenic effects. Either choice ends the game with a cutscene that changes depending on what was selected.