The year is 1975, six years after the events of Bioshock 2. The city of Rapture is in ruins beyond measure. Buildings are collapsing and what were once livable quarters are now loosing life support and succumbing to the ravages of the seas. What buildings are left are still being maintained by The Thinker and it's automatons, but slowly they too are breaking down. With Sophia Lamb gone, and her "Family" in disarray, the population of Rapture is dwindling. Splicers are too focused on fighting one another for their next shot of ADAM to have children and the non-Splicers left are too focused on surviving to bring children into their God-forsaken world. Little Sister are becoming a rarer and rarer sight while feral Big Sisters are increasing as the second generation of Little Sisters are growing older. Still bonded to their grown Little Sisters, the Big Daddies still follow their charges around Rapture; these duos forming dangerous teams.

While it is still anarchy through out most of Rapture, there are still sectors of growth; still hands pulling the Great Chain. Ryan Industrial Park is the last bastion of normalcy and sanity. The few remaining non-Spliced individuals left in Rapture have banded together with The Thinker to save what they can of Rapture before they all drown. Devon Genetics Research Company, a former competitor of Fontaine Futuristics, is now the hive of Splicer activity. Lead by a reclusive and shadowy individual calling him self Revear, the Splicers follow him blindly for their next dose of ADAM. Both are now at opposing goals, and neither can co-exists with the other. Someone is going to go down.

The curtain of the stage that is Rapture is drawing closed. It will be up to those mighty citizens of Rapture to either hoist the great city into glory or tear it apart for the last great treasure that is holds. Ascension or Devastation.