Contrairement aux précédents opus, il n'y a pas de "briefing/débriefing" comme introduction aux missions du jeu mais uniquement des cinématiques (conçues en CGI ou Infographie tridimensionnelle précalculée), moyen employé d'une façon similaire dans Call of Duty 3.
Mais la principale innovation apportée au jeu est l'exosquelette (ou EXO) qui donne un aspect vertical au gameplay du jeu. Un article de Wikipédia, l'encyclopédie libre. Ebenfalls kritisiert wurde, dass der Spieler durch die Wärmebildkamera einer AC-130H auf schwer identifizierbare Personen schießen muss und die Besatzung dies – nach Ansicht der Kritiker zynisch – kommentiert, was das Spiel realistischer wirken lassen soll. Eventually, the group is rescued by Sentinel Task Force operatives, but their leader, Captain Lennox (Bruce Campbell), claims that Oz is the source of the zombie infection. « Parliament » se déroulant sur un cargo militaire accosté sur la Tamise près du Parlement Britannique. The research is carried out in secret, without the knowledge of the employees, in a hidden area known as Sublevel 6.
Back in the quarters, Mitchell, Gideon and Joker celebrate their successful op until they are interrupted by Irons, who proposes they have a toast to a job well done. À l'inverse des précédents Call of Duty qui faisaient suivre 2 ou 3, voire plus, de personnages en même temps, la campagne n'en suit qu'un seul, Mitchell, afin que le joueur ait un plus grand attachement avec lui. Cela pourrait dire que l'histoire de l'Exo-Zombie n'est pas finie.
As he flees, Mitchell manages to escape his exoskeleton and catch up with Irons in his office at the top of the Atlas headquarters. Four years later in 2059, Mitchell and Gideon are dispatched to the irradiated Detroit to find and successfully capture Dr. Pierre Danois (Erik Passoja), the KVA's second-in-command, who reveals that Hades is at Santorini, Greece, where the KVA leaders are holding a conference. While Cormack offers his sympathies to the grieving Irons, the latter offers Mitchell a place in Atlas, claiming that Will told him of the great soldier he was, and that he deserves to fight for an army as effective as he is.
A Call of Duty massively multiplayer online game was also in development. Different types of zombies are present in the game, including Charger zombies that have increased movement speed, and Electro-magnetic zombies (EMZs) that can disable the players' Exo suit in close proximity. On y retrouve les classiques Team Deathmatch, Search and Destroy, Domination, Free For All ou encore Capture the Flag. There are different variants of zombies, including some in Exoskeletons. He praised the iteration of the game set in the mid 21st century, calling it the biggest and most successful departure from what's expected in the Call of Duty series since the Modern Warfare trilogy brought the series into the 21st century.