The story of Mumbai Meri Jaan revolves around a bunch of individuals whose life gets messed up when a tragedy strikes without warning. Rupali, played by Soha Ali Khan, is a reporter who loves life and is awaiting her marriage in two months. Nikhil, played by R. Madhavan is concerned about the environment and thus prefers to travel by train. Suresh, played by Kay Kay Menon is a struggling technician who hates Muslims and Sunil, played by Vijay Kadam is part of the police force, who he despises for being corrupt.
One fine day Suresh and Nikhil who have no connection with each other are travelling in the second class compartment in the local Mumbai train, when a bomb goes off in the first class. Nikhil is now petrified of taking the train again while Suresh blames it all on the Muslims. Sunil and his senior Patil abuse Thomas, played by Irrfan Khan who enjoys calling in bomb scares in Malls. After an old man sufferes a cardiac arrests Thomas feels guilty and stops.
Meanwhile Rupali is devastated to know that her fiancé was one among the dead in the bomb blast and the channel wants to cash in on her emotions. The city and all its people get back to normal after a brief moment of paralysis of shock. The movie is directed by Nishikanth Kamath and produced by Ronnie Screwvala.