Doping is among the most important methods to tune the properties of semiconductors. For dense phase semiconductors, the distribution of dopant atoms in crystal lattices is often random. However, when the size of semiconductors becomes increasingly smaller and reaches the extreme situation as is the case in chalcogenide supertetrahedral clusters, different chemically distinct sites (e.g., corner, edge, face, and core) occur, which can dramatically affect the doping chemistry at different sites and also spatial assembly of such clusters into covalent superlattices. In this work, we use the model system to examine the doping chemistry of Sn4+ and S2- in the Zn-Ga-Se clusters. A series of selenide clusters (undoped supertetrahedral T4-ZnGaSe, S-doped T4-ZnGaSeS, Sn-doped T4-ZnGaSnSe, and dual S- and Sn-doped T4-ZnGaSnSeS) have been prepared with various levels of Sn- and S-doping and with different superlattice structures (OCF-1, -5, -40, and -42). The complex compositional and structural features of these materials are dictated by the convoluted interplay of three key factors: (1) the overall charge density and size/shape matching between clusters/frameworks and protonated guest amines determine the framework topology and the doping levels of Sn4+ and S2-; (2) the site selectivity of Sn4+ is dictated by the local charge balance surrounding anionic Se/S sites as required by the electrostatic valence sum rule; and (3) the site selectivity and doping levels of sulfur is dictated by the location and amount of Sn based on hard soft acid base (HSAB) principle. The cooperative effect of amine-templating and doping by Sn and/or S leads to a rich chemical system with tunable framework compositions, topologies, and electronic properties.