No More Heroes 2: Desperate Struggle is a third-person action-adventure video game for the Nintendo Wii and the second instalment in the No More Heroes franchise directed by Goichi Suda, developed by Grasshopper Manufacture, published by XSEED Games and Rising Star Games.
Three years have passed since Travis Touchdown became the top ranked assassin of the United Assassins Association and walked away. Now, he returns to Santa Destroy and battles Skelter Helter, who seeks revenge on Travis for killing his older brother, Helter Skelter, the former eleventh ranked assassin prior to the first game. After winning the battle and decapitating Skelter Helter, he meets Sylvia Christel again, who informs him that he is now ranked fifty first. The dying opponent interrupts them and warns Travis that he and his conspirators will still have their revenge.
The same night, a group of hired hitmen assassinate Travis' best friend, Bishop Shidux, and throw his head through Travis' motel window in a paper bag. Travis, furious and seeking revenge, asks Sylvia to set up the next fight. Sylvia informs Travis the one who ordered Bishop's death was Jasper Batt Jr., the CEO of the Pizza Batt Corporation and the first ranked assassin. Travis stopped three different attempts by Pizza Batt to expand into Santa Destroy by assassinating the CEO's. In the three years since, with Travis out of the picture, Pizza Batt successfully opened a headquarters in Santa Destroy and purchased practically every business in town. Travis resolves to climb to the ranks to get a chance for revenge on Jasper.
Travis fights and defeats Nathan Copeland, earning him rank fifty. He then meets Charlie Macdonald and his cheerleaders, who transform into a giant mecha called Santa Death Parade. Travis defeat them in his own mecha, the Glastonbury, built by Dr. Naomi and based on a mecha from his favourite anime. He feels remorse for the cheerleaders, realizing that they were harmless, but back-pedals after Sylvia offers to nullify his victory. Before heading off to the next fight, he is challenged by someone ranked below him; college student Kimmy Howell. He defeats her, but spares her life, commenting that he "can't kill a co-ed". He also begins to fight the supernatural, facing Matt Helms and Cloe Walsh.
Sylvia organizes a battle royale with Travis and eleven other assassins. Dr. Letz Shake immediately kills all of the other assassins except for Travis. He is glad for the opportunity to get his revenge on Travis as well, having previously defeating Henry Cooldown and frozen him in carbonite. Travis kills Dr. Letz Shake and defrosts Henry, he also meets Shinobu, who now idolizes Travis and calls him "master". At Sylvia's request, she fought and defeated Million Gunman and New Destroyman for Travis. Shinobu advances on Travis, but he turns away because he feels "like the pervy teacher in a porno". Rejected, she steps out.
Travis fights a gruelling battle against Ryuji and crows triumphantly after Ryuji concedes, but Sylvia kills him in cold blood, criticizing Travis for showing mercy. Henry, suffering from hibernation sickness, fights and defeats Mimmy in a nightmare before awakening. He reconciles with Travis and kills the next three ranked assassins for him. Travis then fights Margaret Moonlight and Captain Vladimir, convincing Sylvia to not destroy the latter's body. After defeating Alice Twilight, the penultimate assassin, he decides his tired of the ranked matches and the UAA. He berates Sylvia, insisting that assassins are humans and they shouldn't have to die for entertainment like it's some kind of video game. He promises to destroy the UAA after exacting his revenge on Jasper.
Travis fights his way through the Pizza Batt headquarters to meet Jasper in his office. Jasper reveals that he was seeking revenge for the deaths of his father and two brothers, the Pizza Batt CEO's that Travis assassinated. Henry enters and helps Travis defeat him. At the end of the fight, Travis kills Jasper and leaps out of the window while Sylvia, riding on a motorcycle, catches him and drops him off at his motel.
Years later, Travis finds Sylvia working at a strip club and pays for private shows from her nearly everyday. He never speaks or reveals his identity, instead opting to listen to her recap the events of the game. On the last day, she breaks down and cries, asking to see his face and hear his voice. Travis finally reveals himself, and says "Let's go, Santa Destroy needs us".