In Tokyo, the relentless pursuit of vengeance drives Yuichi Kimura (Rob Morgan) as he seeks justice after his son Wataru is tragically pushed off a rooftop, leading him to be warned by The Elder (Hiroyuki Sanada) to board a bullet train that night. Meanwhile, under the guidance of his handler Maria (Sandra Bullock), the seasoned assassin Ladybug (Brad Pitt), who battles anxiety and considers himself exceptionally unlucky, is tasked with retrieving a briefcase onboard that same bullet train headed for Kyoto. This mission comes as a result of a prior contract with Carver, who unexpectedly calls in sick.
Onboard the train, Ladybug encounters a young woman known only as the "Prince" (Joey King), a cunning schoolgirl figure manipulating the assassins and claiming to be lucky. Coincidentally, she is the same individual who assaulted Wataru. Compounding Ladybug's troubles, he also runs into Lemon (Brian Tyree Henry) and Tangerine (Aaron Taylor-Johnson), two brothers tasked with escorting the briefcase, which contains a ransom of $10 million, alongside the son of Russian Yakuza boss, White Death (Michael Shannon).
The narrative unfolds with Minegishi, the Japanese mob boss, whose reign was upended by White Death after a brutal coup that left his clan annihilated. As Yuichi hunts for the man responsible for his son’s fall, he instead crosses paths with the Prince, who incapacitates him with a taser.
Chaos escalates as Ladybug inadvertently steals the briefcase from Lemon and Tangerine, only to be confronted by Wolf (Benito A. Martínez Ocasio), a vengeful Mexican assassin holding him accountable for a deadly wedding poisoning, including the loss of his wife—though Ladybug was actually the hero at that event. Their altercation surprisingly ends with Wolf fatally injuring himself.
As the convoluted web of deceit and violence continues, the Prince reveals her Machiavellian motives to Yuichi, including her plot to assassinate White Death, and her desperate measures to hold Wataru hostage through her henchman. Tragedy strikes again when White Death's son meets a similar horrific fate as Wolf's wedding party, escalating tensions among the assassins.
The battle unfolds further as Ladybug struggles against Tangerine and, through a series of misunderstandings and confrontations, inadvertently kills him while trying to protect the Prince. As the remaining players meld their efforts against White Death, an explosive setup leads to a climactic showdown where motives collide amidst a crumbling train.
In a final twist, the Prince's aspirations for power are abruptly halted by fate—an unsuspecting fruit truck, driven by Lemon, brings her reign to an unexpected end. As the dust settles from the havoc wreaked on Kyoto, Maria arrives just in time to extract Ladybug, who finally relishes the thought of escaping the mayhem that ensued on the ill-fated bullet train. This chaotic blend of fate, vengeance, and dark humor leaves an indelible mark on the lives intertwined within the tragicomic web of Tokyo’s underbelly.
