Chev Chelios' (Jason Statham) wild journey begins right after he plummets from a helicopter in the concluding moments of Crank. He is swiftly picked up from the street by a team of Chinese medics. Upon regaining consciousness in a makeshift hospital, Chev faces a shocking reality: doctors are in the process of removing his heart while Johnny Vang (Art Hsu) observes. In a disturbing turn of events, they place his heart into a locked red cooler and install an artificial heart in his chest. During his recovery, Chev overhears plans by the medics to harvest more of his organs, which motivates him to violently fight back and escape.
After realizing his life depends on a yellow battery pack connected to his new heart, he steals a set of clothes and races into a chaotic gunfight. Through sheer determination, he interrogates a thug to discover the whereabouts of Johnny Vang at the Cypress Social Club. With hope clinging to his mind, Chev finds a phone in his pocket and calls Doc Miles (Dwight Yoakam), who provides him crucial information about his AbioCor Artificial heart: once the external battery dies, he only has one hour to live before the internal battery fails. Shortly after, while seeking directions to the Cypress Social Club, a car crash destroys his external battery, pushing Chev to connect jumper cables to himself in a desperate attempt to keep moving forward.
Upon arriving at the club, Chev finds himself in a gripping situation where he saves a prostitute named Ria (Bai Ling) from a brutal customer, only for her to develop an instant infatuation with him. Vang manages to escape with the ominous cooler, leaving Chev seeking vengeance. Much to his astonishment, he encounters his former girlfriend, Eve Lydon (Amy Smart), who has become more adventurous since he last saw her three months prior. A fierce confrontation unfolds between Chev and a gang of Mexican thugs, where he fights valiantly to assert his control, but only a few manage to escape.
As the chaos continues, Chev sustains injuries and is confronted by the police, leading to a perilous escape with Eve in a police car. Adding to the frenzy, he is rescued by Venus (Efren Ramirez), who has Full Body Tourette's Syndrome and claims to know more about Vang. The desperate search leads Chev to the horse racetrack, where he learns he can recharge his heart through friction. In an unexpected and wild display, he engages with Eve on the racetrack amidst cheers from the crowd, revitalizing himself. However, his pursuit of vengeance cannot wait, and he dashes off once again after Vang.
Ultimately, the journey brings him face-to-face with various gangsters and adversaries as he learns about a Triad leader, Poon Dong (David Carradine), who desires his heart for his own use. With tensions escalating, Chev finds himself in a battle against time and ruthless enemies, prompting explosive confrontations, betrayals, and unexpected alliances.
In a climax teeming with action, Chev awakens under dire circumstances, where he faces a resurrected threat in the form of the Verona brothers. As he fights back against El Huron, he musters every ounce of his strength, culminating in a chaotic battle where time and survival are at stake. As the film reaches a twisted conclusion, Chev encounters a mixture of defeat and triumph, ultimately giving a defiant gesture to the audience as the screen fades to black and Crank takes its final bow.
During the credits, there's a glimpse of hope: Doc Miles attempts to reunite Chev with his heart, hinting at a possible resurrection that leaves the audience in suspense.
