The production capacity of compact reactors with micrometer or millimeter-scale channels or tubes is increased by numbering-up. In previous studies, a multi-channel plate type reactor and a multi-tube type reactor (MTR) were developed and applied to extraction and reaction operations. Fluid distribution has often been evaluated to design these reactors, but temperature control, which is critical to the reaction, has not been fully considered. It is important to solve this problem and establish a design method. In this study, computational fluid dynamics (CFD)-based design was performed so as to achieve the uniform flow and temperature distributions among the reaction tubes in the MTR, where an exothermic reaction proceeds in each tube with an immobilized catalyst and the reaction temperature is controlled by a coolant flowing outside the tubes. Effects of multi-tube arrangement of lattice, concentric circles and single circle, shell cross-sectional shape of circle, rectangle and ring, and reaction tubes with or without catalyst-free inert sections on the reactor performance were investigated by CFD. The usefulness of a two-step approach of designing the MTR after designing the double-tubular reactor was confirmed through a case study on parallel reactions.