Throughout the game, you explore the vast Diablo 4 Gold world of Sanctuary, which is now divided into five regions Kehjistan, Scosglen, Hawezar, Dry Steppes, and Fractured Peaks. Each of these regions is in varying states of devastation, influenced by Lilith’s return. The player's journey through these lands will reveal the true extent of her influence on the world and its people.

While Lilith aims to tear the world apart and reshape it into a dark, twisted version of itself, the High Heavens have not been silent. With the fall of Tyrael (the former Archangel of Justice) and the retreat of the angels, the Heavenly hosts are fractured and less united. Their absence leaves a vacuum, and the forces of Hell, led by Lilith, grow stronger. The player finds themselves not only facing Lilith’s army of demons but also dealing with the consequences of the absence of Heaven’s forces.

As the world plunges deeper into chaos, the Nephalem protagonist may find themselves questioning the motivations of the Angels, and how much of Heaven’s crusade has been influenced by their own agendas rather than pure divine righteousness. The player will encounter angels who are either indifferent to the mortal struggle or secretly plotting their own ambitions for control over the mortal realm.

Lilith's ultimate goal is to summon the power of Hell into the world of Sanctuary, effectively bridging the two realms. She attempts to awaken powerful demonic beings and use them to reshape the world, corrupting both the land and its people. Along the way, the player will encounter both allies and enemies who seek to stop Lilith, including factions and organizations like the Zakarum and Sisters of the Sightless Eye, who have their own motives for saving or destroying the world.

A major plot point revolves around a prophecy that foretells the return of a Nephalem, a being who will hold the power to change the course of the world. This prophecy suggests that the cheap D4 materials player’s character, as a Nephalem, is the only one capable of stopping Lilith’s reign of terror and potentially even challenging the forces of Heaven and Hell itself.