We present an operability analysis and a design of a microreactor for hydrogen generation via methane partial oxidation used in unidirectional (UD) and reverse-flow (RF) modes of operation. We show that the reverse-flow operation is more robust with respect to a wide range of changes in reaction parameters. Furthermore, we demonstrate that autothermal operation can be maintained only in the RF mode and not in the UD mode at higher hydrogen throughput or with partial deactivation of the catalyst. On the other hand, increasing the catalyst loading and using the reactor with a higher thermal diffusivity of the solid structure expands the region of stable autothermal UD operation. An analysis of model sensitivity to the kinetic parameters is also performed. On the basis of this, a rational scheme for improved catalyst placement in the RF reactor is proposed.