Agent 47 has been tasked to kill his International Contract Agency handler Diana Burnwood, who has gone fugitive after carrying out a sabotage that crippled the agency. Besides killing Diana, Agent 47 is also called to bring in a young girl named Victoria, who is under Diana's care.

As Diana dies in Agent 47's arms, she gives him a letter and urges him to keep Victoria safe. Reading the letter, Agent 47 empathizes with Diana's cause and decides to rebel against the agency. Now, it's up to Agent 47 to protect Victoria against the agency and the assassins who are after them. He goes on a hunting spree in an effort to save the young girl from peril. Set in beautiful, urban locations with realistic environments, Hitman Absolution is stealth killing at its best with its trademark barb wire execution and silent weapons.