In 2011 a small village in South America is attacked by unknown creatures. Upon inspecting the survivors, a new type of hook worm is discovered and classified as “Alpha-worm”. These parasites cannot be countered with any known medicine and spread through the blood stream of their victims, rewriting their genetic code and turning them into much stronger monsters. They escaped the research facility and the situation quickly became uncontainable, resulting in the drop of an atomic bomb on the site. Since then there have been several contained outbreaks all over the world which have all been stopped by the G.U.I.D.E.-squad, a special forces unit consisting of Ninjas especially trained for these outbreaks.

The game starts in 2015 with another outbreak happening in Tokyo. But as opposed to the previous outbreaks, the parasites are spreading much faster and only a few days after the first infection, the first sky-high level-5-infected are sighted. So once again the team is sent in to deal with the situation. Part of the team: Ken Ogawa.

The player takes on the role of Ken Ogawa and quickly finds himself without his team-mates and betrayed by his own father. Bound to duty but driven by revenge, the player controls him from a classic 3rd-person-perspective through the nine, very long levels. A great part of the game plays similar to Devil May Cry 4 with the player using his three different kind of swords (balanced, slow and fast) as well as a over-sized throwing star to deal with the infected, using the available combos. All the weapons are upgradeable in several stages by using the Blood Crystals that all killed enemies drop. The throwing star also gains additional abilities during the course of the game turning him e.g. into a fire extinguisher or burning projectile. There are also jump-'n'-run-elements included, requiring the player to use wall-walk or swinging on rails to advance through the level.

The game also calls itself an interactive movie and this is where the second core gameplay mechanic comes into play: Quick Time Events. The levels are designed like one big boss fight where the player encounters the final boss of the level right from the start and follows him or is chased by him through hordes of normal enemies, jump-‘n’-run-passages and intermediate-bosses. To keep the action going and looking impressive, the game constantly switches fluently to Quick Time Events, indicated by a quick zoom onto Ken's eye. From this moment on, the player just need to follow the instructions on-screen and watch the carnage unfold. If he fails to hit a button at the right moment, the game rewinds the time back a little but no further than to the start of the Quick Time Event. Since Quick Time Events play an important role, their difficulty level can be adjusted independently from the one for normal gameplay.

At the end of the level, the player is rated based on several factors, gaining him additional Blood Crystals or unlocking new customization options like a new emblem or a suit for Ken.