"Selector Infected WIXOSS" centers around a popular card game called WIXOSS, which has a hidden, darker side. The story revolves around Ruko Kominato, a reserved high school girl who discovers a unique LRIG card named Tama in her deck. LRIGs are sentient cards that act as avatars in the game, and Tama is particularly lively and cheerful. Ruko learns that she has been chosen as a "Selector," a player who can communicate with their LRIG and compete in special battles. The ultimate prize for winning these battles is the fulfillment of a wish, a promise that draws many players into the game.

As Ruko begins her journey, she encounters other Selectors, each with their own motivations and struggles. Yuzuki Kurebayashi, a classmate and skilled Selector, seeks to reunite with her estranged brother, while Iona Urasoe, a mysterious and ruthless player, revels in the thrill of defeating others. The stakes of the game become increasingly apparent as Ruko discovers the harsh consequences of losing. Defeated Selectors lose their memories of the game and their LRIG, and their wishes are twisted into curses. The LRIGs themselves are revealed to be former Selectors who failed in their battles, now trapped as cards and forced to fight for their freedom.

The narrative delves into themes of desire, identity, and the cost of ambition. Ruko's initial reluctance to engage with the game evolves as she becomes more invested in protecting Tama and understanding the true nature of the Selector system. Tama, despite her cheerful demeanor, harbors a deep fear of losing her identity and becoming a mere tool for the game. The relationship between Ruko and Tama forms the emotional core of the story, as they navigate the moral complexities of the battles and the system that controls them.

As the story progresses, the origins of the Selector battles are gradually unveiled, revealing a cyclical and manipulative system designed to exploit the desires of its participants. The characters are forced to confront their own motivations and the consequences of their actions, leading to moments of introspection and growth. The series balances its darker themes with moments of camaraderie and hope, creating a compelling exploration of human nature and the lengths people will go to achieve their dreams.