The level design of the game features a structure similar to that of Hitman: Blood Money and earlier games in the series, as opposed to the linear structure of Hitman: Absolution. Every episode in the game features a sandbox-type environment which can be explored by the player, featuring numerous ways to eliminate targets from accidents to scripted "opportunities" which require multiple tasks to complete. Levels are larger in Hitman, in which the maps in the game are "six to seven times larger than the biggest levels in Absolution". Levels accommodate about 300 non-playable characters (NPCs), with each having different routines and reacting differently to players' actions. Players can save their game anytime during missions. Instinct mode, which was introduced in Absolution, returns in a simplified form, no longer being an expendable resource. A player's mission performance review is rated on a 5-star rating system, influenced by factors such as time taken, number of non-targets killed, whether the player was spotted, whether or not they have been recorded on camera or if bodies were found. Completing challenges in a mission will award players with Mastery Points. Gaining enough mastery points will cause the player to earn a level of Mastery Level, with a total of 20 levels when playing on the "Normal" difficulty setting. As the player progresses through the 20 mastery levels, each level will earn players new items including new gadgets such as weapons, different types of poison and explosives, new agency pick-up locations, or new starting locations. The "Professional" difficulty setting has 10 mastery levels.
IO Interactive introduced a "live component" to Hitman, with new content being delivered regularly in downloadable form. This includes time-limited missions called "Elusive Targets". If a player fails to assassinate an elusive target before the mission expires, or alert the target and allow them to escape, the target will not return. Successful completion of multiple targets yield cosmetic rewards for the player. "Escalation contracts", which are contracts created by the developers, include multiple stages that requires the player to complete certain tasks such as assassinating a target with a specific weapon or disguise or breaking into a safe. Completing a stage will progress through the escalation, and the difficulty will increase with new targets to assassinate, new challenges to comply with or new changes to the level. All additional downloadable content after release will be free of charge. Hitman: Absolution's online Contracts mode also returned in Hitman, allowing players to assign up to five NPCs as assassination targets, set requirements for how to kill them, and share their contract with other players to compete for high scores on. In an interview with PCGamesN, lead online designer Torben Ellert has stated that past Elusive Targets will not be making a return, saying that the quality of the content would not stand up to multiple replays.
47 fulfills several assassination contracts for the International Contract Agency. Though the contracts at first appear to be unrelated, an unidentified man, referred to only as the "shadow client", has covertly coordinated these contracts to attack a secretive organisation called Providence, so that the ICA will appear culpable while disguising his own involvement. The final contracts address the fallout caused by the ICA uncovering the shadow client's actions, and by Providence discovering the ICA's role in the attacks.
In 1999, a man who goes by the alias 47 is initiated into the International Contract Agency, demonstrating exceptional aptitude as an assassin. However, the ICA is unable to verify his background or uncover any information about him. Uncomfortable with having no leverage over 47, the ICA training director, Erich Soders, arranges for 47 to fail his final test despite passing all of the other tests flawlessly. 47's handler and fellow trainee, Diana Burnwood, discovers this plot and helps 47 to pass the test against Soders' order of having him do it alone. Soders reluctantly approves agent status for 47 and assigns Diana as his handler. The events of 47's subsequent career are then shown as a montage of assassinations from the previous games in the series.
In 2019, the shadow client performs an assassination for Viktor Novikov, one of the heads of the international spy ring IAGO, and receives a copy of all of IAGO's gathered intelligence as payment. The shadow client proceeds to use the IAGO files to identify Providence's secret operations. To cover his tracks, the shadow client anonymously discloses to MI6 an impending IAGO auction of an MI6 NOC list, to take place at a fashion show by Novikov's designer label Sanguine. In Episode 1, "The Showstopper", MI6 hires 47 to prevent the sale by assassinating both IAGO ringleaders, Novikov and Dalia Margolis, at the fashion show in Paris, France.
The shadow client sets two more ICA contracts in motion in order to disrupt Providence's activities without exposing himself. He discloses, to a stockholder in the Ether Biotech Corporation, a secret Ether project to develop a deadly weaponised virus. In Episode 2, "World of Tomorrow", the stockholder hires 47 to assassinate Silvio Caruso and Francesca De Santis, the Ether scientists in charge of the project, and to destroy the virus prototype housed at Ether's biolab in Caruso's mansion in the fictitious town of Sapienza, Italy.
The shadow client also discloses an impending military coup d'état in Morocco to Hamilton-Lowe, a construction contractor with lucrative government contracts in the country. In Episode 3, "A Gilded Cage", Hamilton-Lowe hires 47 to eliminate the conspirators behind the plot, General Reza Zaydan and fugitive bank CEO Claus Hugo Strandberg—both secretly Providence operatives—in Marrakesh, Morocco.