The village in South America is attacked by unknown creatures, leading to the discovery of a new type of hook worm classified as “Alpha-worm”. These parasites spread through the blood stream, rewriting genetic code and turning victims into stronger monsters. The situation becomes uncontainable, resulting in the drop of an atomic bomb on the research facility.
The game starts with another outbreak happening in Tokyo in 2015. However, unlike previous outbreaks, the parasites spread much faster, and only days after infection, level-5-infected monsters are sighted. The team is sent to deal with the situation once again, including Ken Ogawa.
As the player takes on the role of Ken Ogawa, they find themselves without their teammates and betrayed by their own father. Driven by revenge, the player controls Ken through nine long levels in a classic 3rd-person-perspective. The gameplay is similar to Devil May Cry 4, with an emphasis on using swords and a throwing star to deal with infected enemies.
The game features upgradeable weapons, including swords and the throwing star, which gain additional abilities throughout the game. Jump-'n'-run elements are also included, requiring the player to use wall-walk or swinging on rails to progress through levels. The gameplay is designed like an interactive movie, incorporating Quick Time Events.
Quick Time Events are a core gameplay mechanic in the game, where the player encounters final bosses from the start and follows them through hordes of enemies, jump-'n'-run passages, and intermediate-bosses. The game constantly switches between normal gameplay and Quick Time Events, indicated by a zoom onto Ken's eye. The difficulty level of Quick Time Events can be adjusted independently of normal gameplay.
The player is rated at the end of each level based on several factors, earning additional Blood Crystals or unlocking new customization options like emblems or suits for Ken.