Sikandar was officially announced in April 2024, with principal photography commencing the following June. It was predominantly shot in Mumbai and Hyderabad and wrapped by March 2025. It is the first film featuring Khan and Nadiadwala since Kick (2014). Sikandar's soundtrack was composed by Pritam, its background score was composed by Santhosh Narayanan, its cinematography handled by Tirru, and was edited by Vivek Harshan.
Sanjay Rajkot, the final heir of the Rajkot dynasty of Gujarat, is known to the people as "Sikandar." He is married to Saisri, also known as Rani Sahiba, a painter. One day, during a flight, Arjun, the son of Minister Rakesh Pradhan, encounters Monica, a former pornographic film actress who has since married and has a son. Arjun threatens to show her past videos to her son in exchange for sex. However, Sanjay, who is also on the flight, intervenes, engaging in a fistfight with Arjun and his bouncers. He ultimately forces Arjun to apologize to Monica. The next day, Minister Rakesh hires Inspector Prakash to arrest Sanjay for attacking his son, personally bribing him for the job. Prakash arrives at Sanjay's mansion in Rajkot, only to find that he is not there. Saisri informs him that Sanjay has already gone to the police station. When Prakash reaches the station, he finds Sanjay there but with his senior officers, who order Prakash to let him go.
Saisri feels that Sanjay is always distant from her. She often notices him forgetting their wedding anniversary and her birthday. One day, she discovers that she is pregnant and tries to share the news with Sanjay. However, at the same time, his quarry manager sells 40 kilos of explosives, which are threatened to be used at a site. This forces Sanjay to rush there to stop the attack. Unbeknownst to him, Saisri follows him to the site, where she gets caught in a bomb blast and is severely wounded. She is rushed to the Hospital, but succumbs to her injuries before she can tell Sanjay about her pregnancy. Prior to her death, she had signed up for organ donation, and her lungs, eyes, and heart are transplanted into patients in Mumbai.
Upon learning that her organs were used in surgeries there, Sanjay sets out to find the recipients and goes to Mumbai. He soon discovers that her lungs were donated to Kamar, an orphaned child from Dharavi, Mumbai; her eyes to Vaidehi Ranga; and her heart to Nisha. Sanjay first encounters Kamar and learns that he suffers from Lung disease due to the severe pollution in his area. The pollution is caused by Virat Bakshi, a businessman who has bought several acres of land to build a mall. However, in an attempt to force the remaining residents to vacate, he uses the land he owns as a dumping ground for Garbage, worsening the living conditions.
Next, Sanjay meets Vaidehi and discovers that she lives with her husband, mother-in-law, and father-in-law. She runs a vadam shop, but her business has stopped receiving orders. She believes her strict father-in-law is the reason, as he holds the belief that women should not work. Finally, Sanjay meets Nisha, who is in the hospital because her donated heart has started to fail. Determined to save her, Sanjay arranges for a doctor from Dubai to guide the local doctors through a video call, which helps to stabilize her condition. He later learns that Nisha was born with a heart condition, which worsened after her ex-boyfriend, Kapil, callously informed her that he was getting married, which caused her immense emotional distress. This leads Sanjay to confront Kapil and beat him up for causing distress.
Before leaving for Rajkot, Arjun spots Sanjay and his group during a speech rally by his father Rakesh. This leads to a cat-and-mouse chase between Sanjay and Arjun, but in the end, Arjun accidentally kills himself by dropping Molotov cocktails on his own car. As Sanjay is leaving Mumbai, he receives a phone call from Rakesh, who vows revenge and says that he will kill all three of the organ donors. Despite this, Sanjay also challenges that he will protect them from him and stays in Mumbai. Eventually, Sanjay helps all three of the organ donors and their families and also develops Mumbai into a better place, allowing Kamar and other children to live peacefully; Vaidehi runs a business after her father-in-law allows her to work; and Nisha lives happily with her family. But soon, Rakesh frames Sanjay in a terrorist bomb attack, which makes the organ donors' trust in Sanjay decrease, but his friends help clear the confusion between them. Soon, Rakesh's henchmen go to attack the hospital where Kamar is hospitalized due to his lung problem, and Sanjay battles with his henchmen and defeats them. The following night, Sanjay breaks into Rakesh’s mansion and beats him. In the end, Sanjay surrenders himself to the Police, but the whole of Mumbai comes to protest about his arrest, and he's set free, thus earning him the title "Sikandar."
