The basics of the oxidation mechanism of different alkanes within zeolites and over molybdenum oxide surfaces were studied employing state of the art computational modelling. It was shown that the constrained environment inside MFI, MFS and MOR induces terminal selectivity on the reaction of 6-, 8- and 10- term linear alkanes, i.e. hexane, octane and decane, respectively. The Monte Carlo (MC) random alkane configuration sampling showed that the oxidation reactivity is driven by the fact that the terminal C atoms of the substrate are more likely to be closer to the zeolites internal walls than the methylene (–CH2–) C atoms. As a confirmation of this, the calculation of kprim/ksec for all the host/guest (alkane/zeolite) systems estimated that the pore effect exerted by the zeolites in the reaction favors terminal products (terminal selectivity). The alkane oxidation over MoO3(010), Fe2(MoO4)3(001) and (110) surfaces involved the activation of a C–H bond of the substrate. The surface calculations were carried out using DFT+U to localize the electrons at a terminal point of the surface. Energy comparison with hybrid DFT (B3LYP) calculations for cluster models of the MoO3(010) surface showed consistency with the DFT+U results. The propane terminal C–H bond activation generated a propyl radical. Transition state structures were found for the adsorption of radical species on MoO3(010) and Fe2(MoO4)3(001) surface and the corresponding energy barriers showed that the adsorption on the former system is favored, which indicates that the Fe2(MoO4)3 surface alone is not a good catalyst for the reaction studied.