In this study, the Eulerian-Lagrangian method is employed to inspect the impact of nanoparticle migration on the hydrothermal and entropy generation features of Fe3O4–water nanofluid in a ribbed-blocked microchannel with two different arrangements. The results are compared with those of the plain microchannel at different volumes of flow rate and nanoparticle concentration. It was found that the nanoparticle migration results in an increase in the pressure drop, friction factor, heat transfer coefficient, overall hydrothermal performance of nanofluid as well as the thermal and frictional entropy generations. In addition, it was depicted that the increase of mass flow rate is associated with the rise of pressure drop, heat transfer coefficient and frictional entropy generation and the decrease of friction factor and thermal entropy generation. Moreover, the augmentation of nanoparticle volume fraction was associated with increasing pressure drop, friction factor, and heat transfer coefficient and the decrease of thermal entropy generation. Finally, it was found that for all the examined cases, the overall hydrothermal performance of the Fe3O4-water nanofluid is better than the pure water.