A series of supported V₂O₅/ZrO₂/SiO₂ and WO₃/ZrO₂/SiO₂ catalysts were synthesized to examine the influence of ZrO₂ nano-domain size on the catalytic active redox and acidic sites, respectively. The zirconia nano-domain was systematically varied on a relatively inert SiO₂ matrix by varying the zirconia content of the supported ZrO₂/SiO₂ catalysts during the catalysis synthesis. HR-TEM revealed that the zirconia nano-domains varied from ~1-5 nm and increased with increasing ZrO₂ content. The catalytically active surface redox vanadium oxide (VO_x) and acidic tungsten oxide (WO_x) sites were deposited by subsequent impregnation onto the supported ZrO₂/SiO₂ substrates containing the ZrO₂ nano-domains. In situ Raman spectroscopy characterization revealed that only 100% dispersed surface vanadia and tungsten oxide species were present in the resulting calcined catalysts and that crystalline V₂O₅ and WO₃ nanoparticles were not formed. Furthermore, these catalytic active sites were found to preferentially self-assemble on the zirconia nano-domains as surface VO_x and surface WO_x species, respectively. The reactivity of the supported surface VO_x and surface WO_x catalytic active sites was found to be significantly influenced by the domain size of the zirconia nanoligand. The surface redox sites experience enhanced catalytic activity with increasing domain size, but the surface acid sites underwent enhanced catalytic activity with decreasing domain size. The inverse responses of surface redox and acidic sites to the ZrO₂ nano-domain ligands reflect the inverse electron requirements of redox and acidic reactions. Thus, tuning the ZrO₂ nano-domains allows control of the availability of electrons to the catalytic active surface redox and acidic sites.