The D-series itself is part of a larger overall campaign of adventures set in the World of Greyhawk campaign setting. The overall campaign begins with the three modules in the Against the Giants series, continues through the D-series, and concludes with module Q1 Queen of the Demonweb Pits. The latter segments of the campaign, including the D-series and module Q1, are set in a vast network of caverns and tunnels called the Underdark.

D2 Shrine of the Kuo-Toa picks up with the party continuing to pursue the drow. The party encounters a kuo-toan rogue monitor who helps them cross a large river for a fee. A party of Svirfneblin (or deep gnomes) approaches the player characters on the other side, and the party has a chance to convince them to help them fight against the drow. As the party travels, signs of the drow are all around; the drow are allowed to pass through these subterranean areas, even though they are hated and feared by the other local intelligent races. The party then moves through kuo-toa territory, ruled by the Priest-Prince Va-Guulgh. If the PCs appease the kuo-toa and respect their customs, the evil kuo-toa are not openly hostile to the party, but will attack if the party gives them a reason. The party learns that the drow and kuo-toa trade with each other openly, but the kuo-toa hate and fear the drow, resulting in frequent skirmishes between the two peoples.