The two-phase model with verified reaction kinetics has been implemented to study numerically dimethyl ether (DME) production in a novel multi-stage fluidized bed catalytic reactor. The single-bed configuration results show that the bifunctional catalyst composition [CuO-ZnO-Al2O3/FIZSM-5] has a pronounced impact on enhancing the reactor performance. Also, the simulation results indicated that the two-bed configuration gives a substantial enhancement of DME yield of 32.67% compared to the single-bed configuration. This yield improvement is also accompanied by significantly improved DME selectivity of almost 100%. The complex interactions of the bifunctional catalyst composition, feed composition and multi-stage configuration play a central role in the extent of the synergy. Interesting two types of maximum phenomena are observed and explanations have been offered. It seeing that synergistic effects have kinetics and thermodynamic strong impact on the development of these phenomena. The loci of these maxima are significant for optimal design and control of multi-bed configurations. It appears that application of multi-stage fluidized bed catalytic reactors is highly promising in DME industry.