A generic methodology is developed to design a heterogeneous catalytic reactor for methanation processes. For the optimization of a heterogeneous catalytic reactor, nonuniform catalyst pellets such as a layered catalyst are considered with respect to reaction type, reactor performance, and component distribution inside the catalyst. Heterogeneous uniform and nonuniform catalyst models were developed to analyze the effect of mass and heat transfer between both bulk phase and catalyst surface and inside a catalyst pellet. Then, concentration profiles of hydrogen and carbon monoxide in the catalyst pellet and along the reactor axis were obtained by analyzing simulation results. It was shown that the application of different types of nonuniform catalyst pellets at a certain number of separate zones within a reactor could produce higher catalyst performance than a reactor with uniform catalyst. Furthermore, it proved a significant decrease of catalyst deactivation behavior such as coking and sintering. Layered catalysts were optimized to maximize an overall reactor performance over the catalyst lifetime, achieving capital cost reduction characterized by reactor size, catalyst amount, and degree of catalyst deactivation. Last, temperature control throughout the reactor operating periods was strategically planned for a reactor operation with distribution of nonuniform catalyst pellets. This methodology can also be usefully applied to the design of heterogeneous catalytic reactors for other processes such as hydro-treating process and cracking process.