毁灭全人类是一款科幻类第三人称动作冒险游戏，充满50年代的科幻影视及文艺作品风格。本作讲述的是邪恶的Furon族的成员——外星人Crypto Sporidium 137，为了得到所需要的人类的基因作为原料来补充族人的DNA原料库，于是乘坐UFO前往地球捕捉地球人，遂遭到了地球人类的反抗。由于是在50年代，地球的科技还不发达，因此要面对这位外星人的入侵人类也是非常吃力的。
Destroy All Humans! follows a long line of high profile console games that have trickled down onto mobile phones, each trying to keep the essence of their parent titles within the constraints of handsets. There seems to be a unwritten rule that applies to all conversions - no matter what the platform - that states that games which are designed from the ground up for that device are much better than those ported across from others. THQ Wireless' adaptation of this B-movie adventure is a perfect case study of how to create a brainless blockbuster, sacrificing refinement in the name of a license.
Taking on the role of a grey-skinned alien warrior named Crypto, it's your job to infiltrate humanity, control them, harvest their brain stems and eventually exterminate them for all eternity. Set in a generic 1950s American town, the mobile version of Destroy All Humans! draws upon the two main gameplay elements of its console counterpart; on-foot action and UFO-based combat.