Following Absolution's reception, the series received a soft reboot in 2016's Hitman, which despite being set in the same continuity as previous installments, returned to a more open-ended style of gameplay and featured a new storyline.

The player journeys to a wide variety of locations, including a mansion, library, strip club, gun store, wrestling arena, courthouse, and hotel before the finishing the game.

Before her apparent death, Diana reveals to 47 that she betrayed the ICA only in order to prevent a genetically-engineered teenage girl named Victoria (Isabelle Fuhrman) from becoming an assassin like 47.

However, his new handler, Benjamin Travis (Powers Boothe), tasked with bringing Victoria back to the ICA at any cost, views 47’s refusal to turn the girl over as a betrayal to the agency and brands him as a traitor.

After the hit, and in payment for the guns, Birdie tells 47 about a man named Blake Dexter (Keith Carradine), who is the head of what purports to be a home defense system against international terrorism.

47, though hard pressed, manages to slip past the authorities staking out a subway station, after which he kills one of Dexter's informants, a mobster named Dom Osmond (Jon Curry), at his strip club.

He then learns that Dexter has hired a group of insidious mercenaries led by one Edward Wade (Larry Cedar) to ensure the capture of Victoria.

Though 47 eventually intercepts and executes all of Wade's associates, Bill Dole (Nicolas Roye), Larry Clay (also James Sie), and Frank Owens (Jeffrey Johnson), Birdie is caught, and threatened by the monstrous Sanchez, betrays Victoria's location in exchange for his life.

After obtaining Lenny's location from a bartender, 47 recovers his 'Silverballer' pistols from a gun store through Birdie's help and moves on to the town of Hope, South Dakota.

Unbeknownst to 47, however, Birdie also makes overtures to the ICA and Detective Cosmo Faulkner of the Chicago PD, culminating in a number of attempts to kill 47 by the Agency throughout the game.

Despite being firmly under the control of Dexter's PMC, 47 manages to eliminate Lenny's gang, the Hope Cougars, preventing them from selling Victoria to a rival weapons corporation.

47 subsequently infiltrates Dexter Industries' laboratory, kills lead members of the science division tasked with examining Victoria, and destroys their research.

At an unlicensed cage fighting match being held on site, 47 kills Dexter's genetically enhanced bodyguard, Sanchez (Isaac C. Singleton Jr.).

While recuperating, 47 is attacked by "The Saints" in a Hawaiian themed motel named Waikiki inn, Travis's personal hit squad, but manages to eliminate them.

47 tracks Victoria to a detention facility within the Hope Courthouse jail operated by corrupt sheriff and Dexter ally Clive Skurky (Jon Gries).

47 evades the Agency and eventually corners Skurky in a Church, who reveals that Dexter and Travis will be meeting to sell Victoria at Blackwater Park, Chicago.

In the final scene, Detective Cosmo Faulkner (Jonathan Adams), who has been tracking 47 since the Terminus Hotel fire, is having trouble discovering 47's identity until Birdie appears and offers to help him, for a price.

[25] In 2023, chief creative officer of IO, Christian Elverdam, said that Absolution "is fundamentally a really good stealth-action game" and that many of the lessons learned in creating it can be seen in the World of Assassination trilogy.

"[49] Eurogamer gave it 7/10 saying "Agent 47 doesn't begin Hitman: Absolution with amnesia, but the six years that have passed since we last took control of him in Blood Money do seem to have dulled his creators' recollections of what made him so popular in the first place.

[9] 1Up.com gave the game an A− saying "Hitman Absolution didn't win me over with its story, but its gameplay maintains a standard of excellence and introduces a level of choice that deserves your attention.

"[41] The New Statesman gave no rating but said "If developers want to win back fans when they revisit established franchises maybe they should look to what made those games popular in the first place and by doing so maybe they'd avoid stepping on a rake or two.

"[55] On 26 March 2013, Square Enix announced that the game had sold about 3.6 million copies at retail, but has failed to reach predicted sales targets.

[61] On 29 May 2012, a cinematic teaser trailer, produced by Square Enix's CGI studio Visual Works, titled "Attack of the Saints", was released.

[62] The trailer's depiction of "gun-toting, PVC and latex-clad nuns being killed in a hail of bullets" sparked controversy over the allegedly sexist portrayal of women.