An agent code-named “Tiger” (Salman Khan) – India’s top spy and an officer of the Research and Analysis Wing (RAW) – is conducting a mission in northern Iraq. Tiger is forced to kill one of his own men who has defected to Pakistan’s spy agency Inter-Services Intelligence (ISI). He subsequently kills many ISI agents in his escape from Iraq, returns to India and reports to his boss, Shenoy (Girish Karnad), in New Delhi.
Tiger is immediately sent on a mission to Dublin to observe a scientist of Indian origin, Professor Anwar Jamaal Kidwai (Roshan Seth), who teaches at Trinity College and is suspected of sharing his findings with the Pakistan defence establishment. Fellow RAW agent Gopi (Ranvir Shorey) accompanies Tiger on this mission.
Tiger meets Kidwai but fails to spend enough time for his observance and instead begins to spend time with the scientist’s caretaker Zoya (Katrina Kaif), who is studying at a local dance academy. He tries to befriend Zoya to extract information, but begins to discover his human side as he grows closer to her. Tiger is attacked and robbed at his residence by a person suspected to be an ISI agent.
Despite several warnings from Gopi to not let any personal feelings get in the way of the mission, Tiger falls in love with Zoya. Tiger asks Zoya for a date and there they both came to know about their feelings for each other. Before telling her his feelings, during a visit to the dance academy, Tiger discovers that Zoya is an ISI agent and she refuses to commit treason on Pakistan when he asks. Instead of killing Zoya, Tiger lets her go.
Some time later, Tiger and Zoya meet again at a UN Foreign Minister’s Meeting in Istanbul when Zoya signals to him using a cryptic message. They decide to leave everything for their love and fool their respective agencies by taking a flight to Cuba, having told their agencies that they are in Kazakhstan. Some years later, their agencies trace Zoya and Tiger due to a CCTV recording. They track them down in Havana, Cuba, and the ISI agents catch Zoya.
Tiger meets Gopi, who is searching for him for RAW, and having lied to Gopi that both Tiger and Zoya intend to return to India and cooperate with RAW, convinces Gopi to save Zoya from the ISI agents. Instead of returning to India, the pair trick Gopi and escape aboarding an aeroplane. Tiger calls Shenoy, who tells him that RAW will find both spies, calling him this time by his real name, Avinash Singh Rathore. Tiger tells Shenoy that they will only return when Pakistan and India no longer need ISI and RAW. In the epilogue, several images of Tiger and Zoya in cities including Venice, Cape Town, Zurich and London are shown, where sightings of them have been reported. But neither agencies have been able to catch them.