After L'Kbreth's Orb was used to bring peace back to the land of Llylgamyn, a new threat emerges in the region. Strange malevolent energies have been spotted beneath the Temple of Sages. These energies - called the "Maelstrom" by the local inhabitants - can be sealed by a person known as the Gatekeeper. Unfortunately, the latter has been imprisoned by a mysterious power or person only referred to as SORN. A party of brave adventurers seeks out the high priest G'bli Gedook, the guardian of L'Kbreth's Orb, who explains to them that they have to release the Gatekeeper and eventually vanquish the evil at its core.

Wizardry V: Heart of the Maelstrom returns to the gameplay concept of the first three installments of the series, abandoning the unusual premise of its predecessor. As in the initial games, the gameplay consists of exploring a vast maze-like dungeon with a custom party created and outfitted in the game's only town. Though visually very similar to their predecessors, the game's dungeon is no longer limited to a square layout. Several tweaks have been applied to the gameplay system, including range rating for all weapons (allowing back row attacks), a more prominent role for the Thief class (who can now hide in shadows, backstab enemies, and open locks), etc.

The game is more puzzle-oriented than the preceding entries, requiring the player to obtain a larger quantity of crucial items needed for its completion. It is the first installment in the series with friendly NPCs who can be encountered in the dungeon and interacted with by typing keywords. Also for the first time, the game allows - but does not require - importing characters from a previous scenario.