In the film the main role is played by Om Prakash Makhija (Shah Rukh Khan), a junior artist in the film industry, set in the 1970's and his sidekick friend Pappu (Shreyas Talpade) who are trying to become big heroes one day. Om’s mother, Bela Makhija (Kirron Kher) who is always seen inspiring and encouraging her son to become a hero. Om is seen as a happy go lucky kind of guy and they talk with each other in a filmy way. Om’s whole family consists of junior artists. Om’s love interest is a rising star and country's heart throb "Dreamy Girl" Shantipriya (Deepika Padukone).
During the premiere of a film, the pallu of Shanti’s sari gets entangled with Om’s hand. Pappu steals an exclusive pass that belongs to Mr. Manoj Kumar to watch the premiere, but have to run out when the real Manoj Kumar appears. While being dragged out of the theater Om manages to get Shanti's attention and he is awed by Shanti’s gaze. One day during the shooting of film, the set catches fire in an uncontrolled manner, Shanti was trapped inside the set, it was Om who rescued her, hurting himself. After the incident, Shanti came to thank him personally, and incidentally she overheard Om’s love for her. They become good friends. Pappu says to Shanti that Om is a big superstar of south India film industry, and even calls her to watch him during a shoot. However, the truth is revealed.
But after that day they often meet each other. Shanti even comes to meet Om hidden in a burkha. Om asks Shanti to bring out her hand and ask for love to anyone she loves. So Shanti goes back to find her love. Next day Om managed to pass security and tried to meet Shanti in her dressing room and he overhears that Shanti is already married to Mukesh Mehra (Arjun Rampal) and is also pregnant. He first said that he wants to keep their marriage under wraps as a married heroine is not accepted in tinsel town. Mukesh also told Shanti that he cannot officially accept this because a rich businessman is financing his upcoming film Om Shanti Om for which he requires 40 lakhs rupees. The real truth was he was getting married to the daughter of the businessman. Om gets heartbroken and tried to avoid Shanti.
One night as Om was sitting near a set of Om Shanti Om (proposed film by Mukesh) he found Mukesh and Shanti driving in to the set. Om crept in the set and saw Mukesh saying Shanti that he has decided to cancel the film and he is going to reveal his marriage with her. He also says Shanti that he will destroy the set. Om, after hearing all these decides to leave the set. In the meantime Mukesh changes his behavior and he holds Shanti responsible for his financial loss and sets fire in the sets of the film so that Shanti dies in the fire. Om saw Mukesh going away in his car. He found out Shanti was trapped inside crying out for help. He tried to help her. But, some of the security guards, who were bribed by Mukesh, beat him up. Even after the beating Om tried to save Shanti, but in vain. In the blast Om is thrown outside and he saw the set getting exploded. Suddenly he got hit by a car owned by Rakesh Kapoor (Javed Sheikh), a well known actor who was rushing his pregnant wife to a hospital. Rakesh takes him to the hospital, but Om dies due to burns as well as the impact of the accident.
The films moves 30 years on after the incident. Om is reborn as Om Kapoor, son of Rakesh Kapoor(he is born right after Om Makhija dies), a burn mark like the Om sign on the wrist can be seen where Om had a tattoo. He is seen as a rising star, a star kid, a rich brat and is also known as OK. While shooting a song for his film, the set's pyrotechnics invoke a phobia, and he is forced to stop shooting. Deciding to move onto the next project, he has his assistant set up a shoot for the next day, who is forced to set it up on-location instead of a set-up. They choose the same burnt studio and set of the old "Om Shanti Om." As soon as he sees it, Om gets the feeling tha the has been there before, and looking around, Om visits the burnt set, and remembers everything about his past life. The Filmfare Award ceremony follows, in which Om wins best actor. During the party that follows, he meets Mukesh again, a popular Hollywood director. He remembers him and, plans to make Mukesh confess to the murder.
Having completely regained his memory, Om goes to meet Pappu and Bela, Om’s mother. He decides to remake the film Om Shanti Om, which was not completed. Mukesh is requested to become the producer of the film. During the audition for the role of Shanti, the audition crew meet Sandy or Sandhya, a look-a-like of Shantipriya. They make a plan; they take Mukesh to the burnt film set to announce the beginning of the film. Here, Om tries to re-act the whole murder with the help of the starcast of the announced film. Sandy often appears to make Mukesh realize that Shanti had turned into a ghost. He gets afraid . But things take a turn and Mukesh comes to know about the plan. Om faces Mukesh and they started fighting. Om first invites Mukesh to a function. Suddenly a chandelier comes & hits his head, making him unconscious. After he wakes up he comes to know that there is no one in the function except he & Om. Mukesh tells to Om that he knows everything about his plan. Suddenly, Sandy comes and starts to talk. Om tries to warn her about Mukesh knowing the plan, but stops, when Sandy starts to speak lines which she was not instructed to speak, and nobody knew about. Sandy appears and reveals that Mukesh came back after burning the set to take care of the body. Mukesh asks her how she knew that. Sandy says that her body was buried right underneath the floor under the chandelier, and that Mukesh was about to die right on the same spot. Om realizes that Sandy should not have known where the body was, and remembers that the painting used to inaugurate the film had burned on its own. He realizes that Sandy was actually Shanti's ghost. Shanti's ghost (soul) kills Mukesh by making a chandelier fall on him. Pappu, Sandy, and Om's manager appear
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