Sands of Destruction is set on a desert world that is periodically destroyed and reborn by an ancient force tied to a power dubbed the Destruct Code and guarded by the four Primal Lords. In the current incarnation of the world, the population is split between humans and anthropomorphic Ferals. Ferals, ruled by the Twelve Beast Lords, mostly treat humans as a slave class. In response to this, two human-centric factions emerge: the World Annihilation Front who seek to find the Destruct Code and destroy the world, and the Golden Lions who oppose the Ferals but wish to preserve the world. To oppose them, the Beast Lords create the World Salvation Committee to defend the current system. The main characters are members of the World Annihilation Front. The protagonist is Kryie, a peaceful-minded young man orphaned from birth who has lived a sheltered existence with friendly Ferals. He becomes allied with Morte, an outwardly cheery woman determined to destroy and restart the world due to it appearing beyond salvation. The pair are joined by Agan Mardrus, a friend of Morte's and member of the Golden Lions; Rhi'a Dragunel, the last of the dragon people tied to the world's beginning and end; and Taupy, a Feral bounty hunter with the appearance of a teddy bear. Naja Gref, initially pursuing the World Annihilation Front before joining their ranks, is a half-Feral who suffers discrimination due to his mixed parentage. Kyrie lives in the village of Barni with his uncle, where humans and Ferals are treated as equals by their ruler the Beast Lord Ursa Rex. One day, Kyrie hears a voice which triggers a power which turns Barni and everyone there into sand, including Ursa Rex. Arrested for Barni's destruction, he is rescued by Morte and the World Annihilation Front. Morte, determined to destroy the world, attempts to sway Kyrie to her side by the oppression of humans under the Ferals. During their travels, they are joined by Taupy, an initially reluctant Agan, and by Rhi'a to observe events. The group, guided by orders from the World Annihilation Front's unknown leader, fights two of the Primal Lords so Kyrie can gain their power. Kyrie comes to care for Morte, and continues hearing the voice pushing him towards his role as the "Destruct". On orders from the World Salvation Committee, Naja pursues them to preserve the remaining Primal Lords.