Two-dimensional vanadia and titania surface clusters were hosted on the walls of the hierarchical pore system of mesoporous silica SBA-15. The topology of the catalyst surface was varied by sequential grafting of vanadium and titanium alkoxides generating an extended library of mixed (VOx)n–(TiOx)n/SBA-15 catalysts. The surface of the catalysts was analyzed by FTIR,UV-vis, Raman, and NEXAFS spectroscopy. Electron microscopy, X-ray fluorescence, X-ray diffraction, and nitrogen adsorption have been applied to characterize chemical composition, micro- and meso-structure of the materials. Segregation of nano-crystalline vanadia and titania particles was excluded by UV-vis, Raman and NEXAFS spectroscopy. Monolayer coverage oftitanium oxide surface species has been achieved in the range between 17 and 19 wt% Ti loading corresponding to 6–8 Ti atoms per nmcat2 and Si/Ti ratios between 3.3 and 2.8. Up to a critical total metal loading, vanadia is grafted on both the silica surface and surface titania species yielding tetrahedrally coordinated vanadium oxo-species characterized by low nuclearity and moderate catalytic activity. A volcano-type dependency with respect to the propylene space-time yield has been observed in the oxidative dehydrogenation of propane. The maximum in productivity of propylene is attributed to a particular surface topology that is characterized by (VOx)n islands embedded in a matrix of dispersed titania species forming an almost complete combined vanadia–titania monolayer on the silica surface.