LISA: THE JOYFUL begins with a flashback to the time in which Buddy is still under Brad's care. Brad kidnaps an unknown man after knocking him out and tying him up, and drags him back into their house. He forces Buddy to kill the stranger in order to teach her how to fight. Flash forward to right after the ending of THE PAINFUL, where a mutated Brad is possibly attempting to kill Buddy. The young girl wakes up and is forced to defend herself against the man who used to care for her, until Buzzo stops the fight and somehow takes Brad with him, leaving Buddy by herself. Buddy heads toward Eastern Olathe with nowhere else to go, and it is at this point that she enters the scene from the end of the second trailer.
- "ATTENTION! HEAVY SPOILERS UP FROM THIS POINT! "
- ―Don't say we didn't warned you, ya slob.
Buddy takes the vaccine and does not transform into a mutant. Using Yado's horn, she culls the mutant hordes and brings a semblance of peace back to Olathe. Buddy buries Rando and proceeds to conceive a son, although the father is unknown. Mutant Brad is present as well, although his role is unknown, along with another grave, which most likely belongs to Buzzo.
Buddy is seen standing in the same valley as the Vaccinated ending, but she is a towering mutant instead. Mutant Brad is seen torn in half, with each half thrown to opposite ends of the valley. Mutant Buddy is seen looming over Dustin's corpse, obsessing over something as all Joy Mutants do.
A short scene with no visuals details the final moments of the Dead Lady at the Joy Lab, where in Yado lays out his plans for Olathe and, finding her "purpose" fulfilled, murders her.
If Buddy goes to see Rando's Corpse using the Joy Mask, an extra scene will be shown after the credits with Marty and a young Brad, where Marty forces Brad to drink alcohol. Marty then says, "Let's go see your sister..." implying that Brad was forced to watch or even join in on Marty molesting Lisa.
If Buddy goes to the hidden Joy Lab Facility, the ending plays a black scene with a dialogue between Buzzo and Lisa, wherein Buzzo mutilates a small animal with his buzzsaw and, at Lisa's behest, mutilates her as well.
Trailer 1The first trailer begins with a young boy with bowl cut and blonde hair awkwardly walking towards what seems to be Lisa Armstrong. The image then turns into Buddy in which she remarks
- "Ready to play?"
- ― Buddy
Buddy is seen to have survived the attack from mutant Brad and is seen with the sword from the ending of the previous game. She is also seen wearing the same clothing as Brad's over her own clothing from the previous game. Further shots show her running across landscapes of burial plots while wearing a mask similar to Rando's.
A second trailer was released on the 8th August 2015. The trailer begins with the words "ALL ALONE", with Buddy walking towards The List with names scrawled in blood, some marked out. A save crow from the first game is seen to the right, showing that JOYFUL inherited many of PAINFUL's mechanics. Buddy is then seen killing more and more people, their corpses littering the hub area, some human, some Joy Mutant.
As she runs to her next destination, she is stopped by a group of men who look like they are wanting to kidnap her, calling her 'Table Scraps' and for his hand to 'Grab that Pristine Meat'. A voice is heard to the right shouting 'STOP Leave her alone' and a the familiar sound of a bell.
- In trailer 2, the names 'Buff Van Dyke','Han Tsunami' and 'Hawk Hollywood' are all crossed out. The three appeared in LISA: THE PAINFUL, and Han and Hawk were killed by Brad, but Buff is a recruitable party member, suggesting that while canonically, Buff was killed in the ending of LISA: THE PAINFUL, he also could have just been crossed off the list when he left his leader position to join Brad's party.
- The part when Buddy is killing more people, the strippers are similar to the workers around Queen Roger's company, Queeny Hideout. And two bands are similar to unused party member.
- The flag resembles Dr. Yado's poncho.