This investigation presents a two-phase analysis of water & ndash;alumina nanofluid flow and heat transfer within a novel four-layer microchannel heat exchanger (MCHE). The counter-current arrangement is adopted and the hot fluid involves the nanofluid, while water is selected as the cold fluid. The two-phase mixture model is used to perform the solutions. On a comparative basis with the base fluid, employing the nanofluid demonstrates a more prominent performance. The nanofluid significantly contributes to the overall heat transfer coefficient (U) enhancement with negligible pressure drop increment. The channel number increment causes severer disruption in the thermal boundary layer resulting in superior U. The effectiveness of the MCHE for all the conditions under study is higher than 0.75. Employing the MCHE with greater channel number results in severer pressure drop. The performance evaluation criterion increases by the volume fraction increment, whereas it declines when the mass flow rate or channel number elevates. (c) 2021 Elsevier B.V. All rights reserved.