[3] The player's goal is to build a base to protect themselves, by planning the layout and defenses, exploring the map, collecting resources and expanding while fighting the local zombie population at the same time.

The player must keep zombies from breaching base defenses and infecting non-defensive structures, especially in tight or overdeveloped areas where a domino effect outbreak can occur.

Much like the player has access to different unit types, zombie types are also varied, ranging between slow, decrepit ones, extremely fast zombies called "Harpies", highly-resistant ones known as "Chubbies" and others, including a massive "Infected Giant" that has high health, speed, and damage that is also highlighted on a minimap, requiring the player to not only have a strong defensive perimeter (with walls, turrets, towers and traps), but also adapt tactics accordingly.

[7] While initially the survivors attempted to establish villages and even fortresses to stave off the zombie hordes, eventually these fall with their technology failing them.

However, a few thousand humans survive, united under the leadership of General-turned-Emperor Quintus Crane, and build and shelter themselves in Empire City, built within a crater that the zombies cannot reach.

Abandoning any attempt to find the cure, scientists turned to create bio-engineered soldiers called Mutants armed with sharpened claws to fight off the zombie hordes.

The campaign ends in Mega York with the player conquering the collapsed Statue of Liberty - now named the Goddess of Destiny - earning Crane's respect and securing the Empire's dominance across North America.