Density functional theory calculations were performed to investigate the mechanism, regioselectivity, and resonance and inductive effects in methylation of nitronate reactions in the gas-phase and in solutions (water, DMF, and CCl₄). The vinylogue extrapolation (VE) approach calculates the resonance effect contributions (ΔE_res) to be −21.79 and −48.53 kJ mol⁻¹ for C-methylation and O-methylation in the gas-phase, respectively, while the inductive effect (ΔE_ind) was calculated to increase the reaction energy barrier (E^‡) by −33.41 and −44.86 kJ mol⁻¹ for the C-methylation and O-methylation pathways, respectively. The larger values of ΔE_res and ΔE_ind for O-methylation suggest that both of these effects serve to increase the E^‡ for O-methylation more than they do for C-methylation, therefore explaining the regioselectivity towards C-methylation. The polar solvents reduce the E^‡ for O-methylation; however, they do not reverse the regioselectivity.