This paper presents the simulation of reactors under different thermal regimes using the most used kinetic models for the simulation of the direct synthesis of DME with the objective of optimizing the coupling between heat and mass transfer. A pseudo-homogeneous and a heterogeneous plug-flow model are developed to simulate isothermal, adiabatic, and isoperibolic fixed-bed (shell-and-tube) reactors for the direct synthesis of DME from CO2 and H-2, enabling the analysis of the limitations by the internal mass transfer. Concentrations, reaction rates, and temperature gradients within the catalyst are assessed. Catalytic efficiency factors are calculated and represented along the reactor tube. The results show that the choice of the kinetic model is crucial for optimal coupling of these functions since it strongly influences the design and sizing of the reactor for synthesis of DME from CO2-rich feedstocks. Therefore, this analysis demonstrates that the direct synthesis of DME can be limited by internal mass transfer, which promotes the DME synthesis at low conversions, therefore requiring particular attention for future reactor optimization.