Thunderball begins with a meeting between Bond and his superior, M, during which the agent is told that his latest physical assessment is poor because of excessive drinking and smoking (up to sixty cigarettes a day). M sends Bond on a two-week treatment at the Shrublands health clinic to improve his health. At the clinic Bond encounters Count Lippe, a member of the Red Lightning Tong criminal organisation from Macau. When Bond learns of the Tong connection, Lippe tries to kill him by tampering with a spinal traction machine. Bond, however, is saved by nurse Patricia Fearing and later retaliates against Lippe by trapping him in a steam bath, resulting in the Count's second-degree burns and a week's stay in hospital.
The Prime Minister receives a communiqué from SPECTRE (SPecial Executive for Counter-intelligence, Terrorism, Revenge and Extortion) explaining that the organisation has hijacked a Villiers Vindicator and seized its two nuclear bombs, which it will use to destroy two major cities unless a £100,000,000 ransom is paid. This is SPECTRE's Plan Omega. SPECTRE is headed by criminal mastermind Ernst Stavro Blofeld. Count Lippe was dispatched to Shrublands to oversee Giuseppe Petacchi of the Italian Air Force, at the Boscombe Down Airfield, a bomber squadron base. Although Lippe was successful, Blofeld considered him unreliable, because of his childish clash with Bond and, as a consequence, Blofeld has Lippe killed.
Acting as a NATO observer of Royal Air Force procedure, Petacchi is in SPECTRE's pay to hijack the bomber in mid-flight by killing its crew and flying it to the Bahamas. Once there, Petacchi is killed and the plane, with bombs, are taken by Emilio Largo (aka SPECTRE Number One) on board the cruiser yacht Disco Volante.
The Americans and the British launch Operation Thunderball to foil SPECTRE and recover the two atomic bombs. On a hunch, M assigns Bond to the Bahamas to investigate. There, Bond meets Felix Leiter, seconded to the CIA from his usual role at Pinkertons because of the Thunderball crisis. While in Nassau, Bond meets Dominetta "Domino" Vitali, Largo's mistress and the sister of the dead pilot Giuseppe Petacchi. She is living on board the Disco Volante and believes Largo is on a treasure hunt, although Largo makes her stay ashore while he and his partners hunt hidden treasure. After seducing her, Bond informs her that Largo killed her brother; Bond then recruits her to spy on Largo. Domino re-boards the Disco Volante with a Geiger counter to ascertain if the yacht is where the two nuclear bombs are hidden. However, she is discovered and Largo tortures her for information.
Bond and Leiter alert the Thunderball war room of their suspicions of Largo and join the crew of the American nuclear submarine Manta as the ransom deadline nears. The Manta chases the Disco Volante to capture it and recover the bombs en route to the first target. An undersea battle ensues between the crews, while Bond fights Largo. Bond, now very weak from his efforts to disable the bombs, tries to get away, but Largo corners him in an underwater cave and easily overpowers him. Before Largo can finish Bond off Domino shoots him with a spear gun. The bombs are recovered and Bond is sent to hospital with Domino.