In Academy City, a place where supernatural abilities are recognized as a scientific discipline, a hidden world operates beneath the surface of its peaceful, high-tech streets. This is the Dark Side, a shadowy realm where unofficial missions too dangerous or disgraceful for public knowledge are carried out. The manga focuses on ITEM, an elite, four-girl unit that functions as one of the most effective teams operating in this criminal underground.

The group is composed of unique and powerful espers. The leader is Mugino Shizuri, one of only seven Level 5 powerhouses in the entire city, whose destructive Meltdowner ability allows her to fire particle beams that disintegrate matter at a molecular level. She is joined by Takitsubo Rikou, whose support ability lets her track the unique AIM diffusion fields emitted by other espers, making escape nearly impossible for their targets. The team's frontline fighter is Frenda Seivelun, a girl with a cheerful demeanor and a talent for combat using bombs, explosives, and various traps. Rounding out the group is Kinuhata Saiai, who uses her power to freely manipulate nitrogen to create a dense shield of air around her body, acting as the team's impregnable defender.

The story begins as this well-oiled machine of assassins and saboteurs takes on a new member, a girl named Hanano Choubi. What initially seems like a routine personnel change draws ITEM into a much larger conspiracy brewing beneath the city. Their missions quickly escalate from standard dark-side exterminations to infiltrating corporate headquarters for sensitive data and hunting down double agents trying to flee the city.

The narrative is constructed through distinct arcs that build toward a devastating conclusion. The first major storyline, the Enemy Item Arc, introduces the team and their dynamics as they navigate the treacherous politics of the Dark Side. This is followed by the Honey Queen Arc, the Dark Justice Arc, and the Mugino Family Arc, each escalating the danger and delving deeper into the personal histories and motivations of the main characters.

A central event during this period is The Colosseum, an underground entertainment arena where espers are forced to fight to the death for the amusement of wealthy spectators, with a grand prize of 15 billion yen. Seeing an opportunity amid the chaos, ITEM launches a bold operation to storm the Colosseum and seize the prize money, a heist that puts them directly in the crosshairs of powerful underworld figures. As the girls live freely in the darkness, taking on missions that others cannot, their story becomes one of violent encounters, fragile friendships, and the slow, creeping dread of an inevitable, terrible incident that will eventually shatter their group forever.