Decades ago, Dr. Piotr Litvenko (Ciarán Hinds) led a secretive program that aimed to develop clone soldiers—so-called "perfect assassins" endowed with enhanced strength, intelligence, and reflexes, while being incapable of feeling emotions such as guilt or remorse. After grappling with a crisis of conscience, Litvenko vanished, leaving his daughter Katia behind. In the wake of his disappearance, the government shut down the program, and the remaining agents began to drift away. Despite numerous attempts to revive the program, the modified agents continued to perish, leading to a singular goal: tracking down Litvenko, the key to reincarnating the program.
Enter Agent 47, a formidable ex-agent who is hell-bent on locating the official tasked with finding Litvenko to exterminate him and his team. Right before eliminating the official, Agent 47 extracts vital information regarding Katia’s whereabouts. While his intentions appear to target Katia, the reasons remain shrouded in mystery. Meanwhile, the organization known as the Syndicate International catches wind of the official's assassination and mobilizes its resources to find Katia beforehand.
Years later, an adult Katia (Hannah Ware) resides in Berlin, obsessively seeking her father, haunted by anxiety and possessing acute sensory awareness—capable of perceiving sounds and sights well beyond the normal range. One day at a subway station, she meets a mysterious man named John Smith (Zachary Quinto), who warns her that Agent 47 is approaching to kill her and offers protection while hinting that he holds information about her father. Just as 47 locates them and strikes, Katia narrowly escapes, although she suffers a graze from a sniper bullet.
In a hotel, Katia shares her map of clues searching for her father while Smith reveals his connection to Syndicate International and provides insights about Litvenko's health—specifically, his stage 3 lung cancer, age, and that he speaks several languages including Hindi. With this new information, Katia deduces that her father would reside in a warm climate conducive to growing orchids, a country where Tamil is an official language, and advanced medical treatments are accessible. Just as she starts to pinpoint the location, Agent 47 bursts into the hotel room, fatally injures Smith, and knocks Katia out cold.
Upon regaining consciousness, Agent 47 reveals to Katia that she is also an Agent, even more advanced than himself. He reveals her real name—"Quatre-Vingt-Dix," French for "90"—and trains her to harness her heightened senses for combat. As both prepare to confront the forces of the Syndicate, Agent 47 discloses that they were both products of the same program developed by her father.
Things take a turn when they face off against Smith, who, surprisingly, has survived the gunshot thanks to genetically engineered internal armor. Frustrated with being designed as a killing machine, Katia struggles with her identity. After a brief clash, they manage to escape with Katia insisting that Agent 47 must promise not to harm her father. They finally uncover that Litvenko is in Singapore, further unraveling the Syndicate's desperation to find him, as they aim to reconstruct the Agent program.
Once in Singapore, they find an ailing Litvenko, who apologizes for leaving Katia behind, stating he only wished to keep her safe. He refers to 47 as her "brother," indicating familial ties between them. Just then, they are assaulted by Syndicate soldiers, leading to chaos. In a dramatic turn, Litvenko is captured, but not before getting an explosive-rigged inhaler from 47.
At the Syndicate International headquarters, Smith tortures Litvenko as powerful director Antoine LeClerq (Thomas Kretschmann) oversees the proceedings. Despite torture, Litvenko stays steadfast in his refusal to restart the Agent program. Meanwhile, Katia sends a helicopter crashing into the building while Agent 47 infiltrates disguised as a firefighter. Together they engage in a fierce battle against Syndicate security.
The confrontation escalates with 47 once more battling Smith, ultimately using electricity to defeat him. On the rooftop, the fight continues as they clear the remaining Syndicate forces, only to see LeClerq escape with Litvenko via helicopter. Mid-air, Litvenko detonates the explosive inhaler, ensuring the Syndicate won't pursue Katia anymore.
Afterward, 47 confirms the demise of his first target to Diana—LeClerq—while she inquires about the second target: Katia. In a shocking moment, he chooses to drop the phone instead of completing his mission. As they plan to leave, they encounter Agent 48, a doppelgänger of 47, who ominously shares, > “Diana says ‘Hello’,” before a fierce gun battle ignites.
In a mid-credits scene, Smith, his body electrocuted and altered, awakens with ghostly white hair and a starkly pale complexion, hinting at further chaos to come.
