The story begins in 1372 DR with the player character being sent by Lady Aribeth to recover four monsters needed to make a cure for the Wailing Death, a plague that is sweeping the city of Neverwinter. It is part of the Forgotten Realms campaign setting. Neverwinter is a city on the Sword Coast of Faerûn.
The first and final chapters of the story in the official campaign deal with the city of Neverwinter itself, but the lengthy mid-story requires the player to venture into the countryside and then northward to the city of Luskan. In the original NWN scenario supplied with the game engine, the player is single-handedly responsible for defeating a powerful cult stopping an insatiable plague thwarting an attack on the city of Neverwinter, and many other side quests. Play centers on the development of a character that becomes the ultimate hero of the story.