Like previous Yakuza games sidestories are often available between story missions. Even more dangerous Prototypes will appear as bosses during the storyline. In addition to zombies they will also face mutants, such as the quick and agile Monkeyboy or the zombie-summoning Cry Baby, who are stronger and will require different tactics. While inside the quarantined areas of Kamurocho the player can be swarmed by zombies at any time, with more than twenty attacking at once. Each character can equip up to four weapons at a time, from pistols with unlimited ammunition to wide-spread shotguns, powerful anti-armor rifles, and incendiary grenades.

The game also has a radically new combat engine, as the living dead can easily shrug off kicks and punches. Yakuza: Dead Souls is the sequel to Yakuza 4, taking place one year afterwards but with a decidedly more fantastic premise. As the city burns four men search for answers: Shun Akiyama, the enigmatic moneylender from Yakuza 4 Goro Majima, Leader of the Tojo clan's Majima family Ryuji Gouda, exiled former-chairman of the Omi Alliance and antagonist of Yakuza 2 and the Dragon of Dojima, Kazuma Kiryu.

The district of Kamurocho has survived gang violence, terrorist bombings, and open mafia war, but the latest threat may be the one that finally destroys the district for good: a zombie apocalypse.

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