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Dhoom reinvents the classic cops and robbers tale for the 21st century. Fast bikes, big action, and non-stop fun make for a thrilling story.

The tale begins in Mumbai where a gang of robbers is sweeping through the city. Officer Jai Dixit (Abhishek Bachchan) is brought in on the case and he is on the trail of the robbers - a gang led by Kabir (John Abraham). Jai ropes in the services of Ali (Uday Chopra), a carefree garage mechanic and a prodigious biker. With fast bikes, big action, DHOOM reinvents the classic cops and robbers tale.—Official Source

In the city of Mumbai, a motorbike gang starts breaking into banks, armored cars (carrying cash) and other public places and vanishes onto the Western Express Highway. Shekhar Sharma (Manoj Joshi) is the investigating officer on the case, who is not able to make any progress.

Assistant Commissioner of Police Jai Dixit (Abhishek Bachchan), a no-nonsense cop, is called onto the case. Jai lives with Sweety (Rimi Sen) his wife (who is a veterinarian) who is very suspicious of him. Sweety wants to have a baby with Jai, but Jai is always called to work as soon as Sweety tries to get intimate with him. Jai learns from Shekhar that the bikers are a gang of 4 riding high-performance bikes.

Ali is a street bike racer (and aspires to speak in English but doesn't manage to get the diction and grammar right) who is struggling in the matter of attracting women. Ali befriends Sweety after he saves her dog from an accident. He dreams of a family with her, but those dreams are crushed when he finds Sweety is wedded to Jai. Jai finds Ali at his home (and learns that Ali owns a bike garage in Mumbai) and later finds his photo in a list of suspects that Shekhar shared with him (as he drives a high-performance bike).

Jai and his team suspect Ali (Uday Chopra) to be part of the biker robbery gang. Jai visits Ali and investigates him to figure out whether he is part of the gang or not. Jai's theory is that the gang drives imported bikes and hence must be part of a biker club in the city. Jai asks Ali to get him a fast new bike. Jai arrests Ali after Ali takes him to a Muslim area gray market. Jai had beaten up some goons at the gray market who tried to bully him. The whole gang attacked Jai with crude weapons, and Ali helped him escape on his bike. Ali demonstrates his driving skills during the escape which convince Jai that Ali is part of the gang.

But a robbery takes place while Ali is in Jai's custody and Jai is convinced that Ali is not part of the gang. The biker gang uses a container truck on the highway to hide inside it and escape all roadblocks. The bikers work as pizza delivery boys to hide their identities. Now Jai wants Ali to help him catch the biker gang. All the robberies were near the western express highway (and within 2-3 minutes of the highway itself for fast getaway) and Jai is able to predict the location of their next heist at BKC in Mumbai. Jai says that the gang has stuck 5 times in the past 20 days, so their next heist will be soon.

Kabir (John Abraham), the leader of the gang, and is super smart and knows how to fly under the police radar. His gang includes Rohit, Rahul and Tony (Amir Farid). Karan admonishes Rahul when he buys a flashy new car and says that the thieves need to maintain a low profile.

Karan sees Jai doing the recce of his next robbery location and knows that police are getting closer. Kabir strikes in the same location but at a different bank than what Jai was watching. Jai and Ali are distracted by Kabir's gang member Sheena, who pretends to be a damsel in distress. Jai follows on Ali's bike and even manages to get one shot at Kabir and injure another gang member Rahul (Aarav Chowdhary). Rahul is rescued by Kabir and their gang get away on their NO2 spiked bikes. But Jai gets their loot and Rahul's bike for analysis.

The gang members want Kabir to take action against Jai. Kabir eventually calls and taunts Dixit, claiming that Dixit can't catch him even if he is right in front of him. Kabir wants Jai to leave the case if Jai can't stop him despite knowing the time and place of the next robbery. Kabir says that if Jai manages to foil his plans, he will surrender and serve his time in jail. Despite elaborate planning Jai fails to stop Kabir and his gang from making away with the loot, but he manages to shoot down one gang member Rohit. Their target was the Chief Minister's charity function where Sheena was performing. Karan managed to escape by setting the entire concert on fire, and Ali, whose job was to keep the bike ready for the chase, was busy rescuing Sheena.

Through Rohit Jai figures that the gang works at a local pizza parlor. Jai believes that Ali sold him out, which is why he could not catch the biker gang in action. Jai publicly beats Ali for selling him out and breaks his alliance with him. Jai resigns from the force.

Kabir then lures Ali into his gang as a substitute for Rohit (Rohit Chopra), the gang member who was killed by Dixit. Ali falls in love with Sheena (Esha Deol), another gang member. The gang later goes to Goa to perform one last big heist before disbanding forever. Kabir sets his eyes on the largest casino in all of India. Kabir and his gang swiftly loot the casino on New Year's Eve, but they soon realize that Dixit has led them right into a trap. It is revealed that Ali was working for Dixit the whole time. Kabir manages to escape from Jai at the casino with his mates.

Kabir goes back to the gang's truck where Ali has kept Sheena bound and gagged. Kabir then viciously beats up Ali for his betrayal, but Ali is saved by Dixit's timely arrival at the scene. The gang flees, except for Sheena, while Dixit and Ali give chase to Kabir. They kill all the other gang members except Kabir, who tries to escape on his bike. He is cornered by Dixit and Ali with nowhere to go. Kabir decides to take his own life rather than let Dixit arrest him, and he rides his bike over the edge of a cliff into the water to his death. The film ends with Dixit and Ali arguing with each other, albeit in a friendly way.