During a dark night in Iraq, an American journalist types a warning message to CIA before he is slaughtered by some guards. Abu Usman is the head of ISC, a terrorist organization which kills American journalists. While carrying a rally in Ikrit, Usman is shot in the arm by the Iraqi Army. He is taken to the city hospital. Abu Usman holds hostage of the Indian and Pakistani nurses and makes the hospital as his center. USA decides to launch an airstrike at the city to kill Usman. Indian nurse Maria calls the Indian Embassy of Iraq, informing about the incident. The chairman of the RAW, Shenoy, has talks with CIA who give him 7 days of time to rescue the nurses after which they will hold the airstrike. Shenoy feels that only Tiger would be able to rescue the nurses and that too within a period of 7 days. Eight years after the events of Ek Tha Tiger, Tiger and Zoya are living in Innsbruck, and have a son, Junior.
Several days later, Tiger is called by Shenoy. He meets his deputy Karan who informs him about the abduction of nurses. Tiger has the whole information recorded in his pen drive but refuses to carry the mission as he thinks RAW would not forgive him. But after Zoya insists him, he sets to carry the mission. Tiger travels to Syria. Karan suggests him the plan and members but Tiger refuses and brings his own gang of RAW members consisting of Azaan, a sharpshooter, Namit a bomb-defuser, and Rakesh a senior- citizen but expert hacker. They reach an oil refinery controlled by Baghdavi and carry out the plan but face difficulty after the arrival of Firdauz, who has the duty of checking the workers. In the hospital a Pakistani Nurse Sana gets caught while escaping by an ISC member which results in her getting shot. One day, Tiger spots Hassan, a child sent by Abu Usman as a human bomb whom Tiger rescues and flees with the help of Zoya and her ISI team members Abrar and Javed.
That night, Tiger and his gang set fire in the refinery and pretend to get burned so that they are taken to the hospital. Baghdavi reluctantly agrees to send them after assertion of Firdauz. En route to the hospital, they are joined by Zoya, Abrar and Javed. Firdauz reveals that he is a secret RAW agent working from the past 25 years. They go the hospital while Zoya leaves Tiger to first kill Baghdavi and his troops which she does with the help of some Syrian girls.
At the hospital, Tiger orders Rakesh to poison the food served to Usman's troops. On the day of the airstrike, the troops are food poisoned and Usman is angry. Tiger fights and defeats the troops and rescues the nurses from the hospital. Abu Usman holds Zoya in hostage which causes him to surrender. Everyone is captured by ISC and Tiger is tortured in a poison chamber. Tiger flees from the chamber and rescues the nurses and his team but Azaan is shot while fighting. He requests Captain Javed to raise the Indian Flag after the success of the mission. As they escape, they are joined by Firdauz who crashes an oil tanker which kills ISC members. Tiger disguises everyone in the execution robes of American journalists in order for a safe passage out of Ikrit.
Tiger leaves to rescue Zoya. As he tries to break the chains in the tunnel, he is beaten up by Usman but Tiger stabs and wounds him in a fierce encounter and moves to rescue Zoya. Zoya insists Tiger to leave her for the verve of Junior. A missile blows the chamber. In the bus boarding back to India without Tiger, Javed raises Indian and Pakistani flags above the bus keeping Azaan's promise and also as a signal of friendship, meanwhile Firdauz takes Usman to a desert in his car and shoots him dead.
One year later, Shenoy is called by Tiger from Greece. A flashback shows that Tiger broke the chain and rescued Zoya. Tiger and Zoya have adopted Hassan. Though Tiger goes into hiding once again due to his belief that the RAW will never let him go, he assures Shenoy that he will always be there for his country in trouble.