Group I-II-V-VI semiconducting Cu12- xM xSb4S13 (M = ZnII, CdII, MnII and CuII) substituted tetrahedrite nanostructures remain a new class of multinary materials that have not been widely explored yet. Having different ions, the formation process of these nanostructures always has the possibility of formation of cross nucleations. Minimizing the reaction time, herein, a predominantly thermodynamic control approach is reported, which decouples the quaternary nucleations from their possible cross nucleations. As a consequence, possible cross nucleations were prevented and a series of nearly monodisperse intriguing substituted tetrahedrite nanostructures were formed. The possible LaMer plot for the single- and multimaterial nucleations is also proposed. Further, bandgaps of all of these new materials are calculated, and preliminarily, the applicability of these materials is tested for photoelectrochemical water splitting.