In "Sands of Destruction," the world is dominated by beast-like creatures known as Ferals, who subjugate humanity and maintain control over the planet. Humans live in fear and oppression, with their lives dictated by the Ferals' strict hierarchy. The narrative centers on Kyrie Illunis, a young human with a mysterious ability to summon destructive power, and Morte Ashera, a member of the World Annihilation Front, a group dedicated to overthrowing the Ferals and destroying the world to end humanity's suffering.

Kyrie's life changes when Morte recruits him into the World Annihilation Front, revealing that his latent power could be the key to their mission. Together, they embark on a journey to locate the mythical "Dual Blade," a weapon said to possess the ability to destroy the world. Along the way, they are joined by other characters, including Toppi, a Feral who opposes the oppressive system, and Liuba, a human girl with her own tragic past tied to the Ferals' cruelty.

As the group travels across the world, they encounter various factions, including the Ferals' ruling class and human resistance movements. The story explores themes of oppression, rebellion, and the moral complexities of seeking destruction as a means of liberation. Kyrie struggles with his role in the mission, questioning whether annihilating the world is truly the solution to humanity's plight. The narrative builds toward a confrontation with the Ferals' leaders, culminating in revelations about the origins of the world and the true nature of Kyrie's power.

The series balances action, character development, and philosophical undertones, presenting a world where the lines between right and wrong are often blurred. The main characters' motivations and relationships drive the plot, with each member of the group contributing to the overarching goal while grappling with their own personal struggles. The story concludes with a resolution that ties together the themes of sacrifice, hope, and the possibility of a new beginning.