This study investigates the relevant heat and mass transfer phenomena occurring at the different scales in a packed bed (membrane) reactor for the direct conversion of CO2 to dimethyl ether (DME) via the implementation of 2D heterogeneous reactor models. Intra-particle diffusion limitations were found to be relevant for particle diameters larger than 1 mm and temperature above 220 ⁰C, such that the catalyst efficiency drops down to 50% and 5% for the Cu/ZnO/Al2O3 and the HZSM-5, respectively, in the most critical conditions (i.e., 270 ⁰C and Dp of 10 mm). A component-specific Thiele modulus-efficiency correlation was developed based on the results of the rigorous particle model to account for pore-diffusion limitations without having to solve a complex heterogeneous reactor model. This correlation shows the typical behavior reported in literature for power law kinetics and accurately predicts the reaction performance with deviation of less than 5% for values of the Thiele modulus lower than 2. In the packed bed membrane reactor (PBMR), the concentration polarization (CP) also showed to affect the reactor performance. The concentration of water at the surface of the membrane selective layer was found to be up to 64% lower than the concentration in the bulk phase, hindering the effectiveness of the membrane separation. To account for this phenomenon via a simplified approach, a Sherwood-type correlation was developed to determine a CP mass transfer coefficient, based on the results obtained via the rigorous 2D PBMR model. Such correlation showed to predict with high accuracy (i.e., errors lower than 5%) the effect of the CP on the PBMR performance. Differently from the pore diffusion and CP phenomena, the intra-particle heat transfer, the particle–fluid mass and heat transfer as well as the axial dispersion were found to have a negligible effect on the reactor behavior. Finally, given the relevant mass/heat transfer phenomena, this study proposes further reactor optimization strategies, such as the reduction of the zeolite loading in the bifunctional catalyst bed by ca. 90% with respect to what is reported in literature.