It begins with a plane crashes in the Atlantic Ocean. Jack,the only survivor, swims towards the lighthouse. Inside of it is a bathysphere that takes him to rapture. Jack was later contacted by Atlas,who explains that it was built by Andrew Ryan,a business magnate and has been rival to Frank Fontaine,Atlas' employer and after his apparent demise,The plasmid-enhanced humans,known as the Splicers wage war against one another.
Altas tells Jack to use the ADAM to give him super-powers. After He encounters one Little Sister,whom came back after Polygon Man's defeat. Tenenbaum insist Jack to spare more than one Little Sister and remove the sea slugs out of them. Jack cures the Little Sisters one by one and fought his through,including doctor J.S. Steinman & musician Sander Cohen
Jack enters Ryan's office where Ryan reveals that he is Jack's illegitimate father,whose mistress sold him as an embryo to Fontaine,who had Tenenbaum rapidly age Jack into adulthood,turning him into an obedient assassin,but he was smuggled to the surface with false memories of a normal life. Ryan also reveals that Fontaine was the one who brought down the plane and none of them had Atlas in their records. Ryan commands Jack to beat him to death,which he did. Atlas took over the city,revealing himself to be Fontaine.
Jack was quickly saved by Tenenbaum,who helps remove Fontaine's mental condition,including one that could stop his heart. Jack pursues Fontaine to lair,where Fontaine transforms himself into a hulking humanoid creature by injecting himself with ADAM. Jack drains the ADAM out of Fontaine,but gets knocked out. Fontaine was about to kill Jack,but the Little Sisters,whom Jack saved,stabs him with several needles to suck out his ADAM,killing him.
Jack & Tenenbaum takes the Little Sisters back up the surface and adopt five of them.