Kate is an assassin and expert sniper who eliminates targets chosen by her trusted mentor and handler, Varrick. After she was left orphaned as a child, Varrick raised her as a father figure, giving her extensive training in weapons and combat and eventually inducting her into his private team of wetwork specialists.
As the film opens, Kate is in Osaka to kill an officer of a powerful yakuza syndicate, readying herself with her rifle in a vantage point. The syndicate member steps out of his car and presents himself as a target, but Kate resists taking the shot because a child has unexpectedly accompanied him. She ultimately shoots the target at Varrick's insistence. While Kate's assignment is a success, this breach of her personal code to not kill in the presence of children leaves her in emotional turmoil. She tells Varrick that she will do one final mission, and then retire so she can start a new life.
Before the final mission, Kate meets a charismatic stranger, Stephen, at her hotel's bar. The pair share a bottle of wine and have sex in her room. Later, while preparing her sniper's nest, she starts getting symptoms of dizziness that cause her to miss the shot. Kate realizes that Stephen poisoned her, and after crashing her car, wakes up in a hospital to learn that she has acute radiation poisoning caused by Polonium-204 and only twenty-four hours to live. She steals injectable stimulant drugs and a gun and sets out to exact revenge on whoever poisoned her.
Kate tracks down Stephen and his girlfriend, and learns that they were strong-armed into poisoning her by Sato, a yakuza affiliated with the Kijima crime family. Kate finds Sato at a luxury restaurant and kills him along with dozens of armed yakuza. Desperate for information about the reclusive, well-guarded Boss Kijima, who she thinks might be behind the poisoning, she kidnaps Ani, Kijima's biracial niece. Kate realizes that Ani is the girl who saw her father die during the Osaka mission.
While Kate initially only wants to use Ani as bait to lure Kijima out into the open, she decides to become her protector upon learning that Ani's family wants to kill her as part of an internal power struggle, led by Kijima's corrupt advisor, Renji. Kate uncovers more clues about the Osaka mission and realizes that her trust in Varrick may be misplaced after tracking down Kijima, who reveals that Renji made a deal with Varrick to incorporate his team into the syndicate in exchange for killing Kijima and all of his blood relatives. Kijima, aware that Kate is close to death, provides her with a small army of his men to assault Renji's headquarters.
After a fierce gunfight, all of Renji and Varrick's men are killed, and Kijima personally beheads Renji for his betrayal. Kate locates Varrick, who is holding Ani at gunpoint. The two have a fast draw and Varrick is fatally shot in the stomach. Ani then helps Kate walk outside to the roof, where Kate, finally at peace with herself, dies.