With the rapid growth of information technology and the evolution in the use of microelectronic chips, these components are facing major challenges of high heat dissipation and inhomogeneous heat flux. To address the hotspot issues, a combination of microchannel heat sinks (MCHS) with cavity-rib designs and supercritical fluids is a potential solution. This study compares the thermo-hydraulic properties of water and supercritical carbon dioxide (sCO2) under various boundary conditions and hotspot locations during non-uniform heating. The results showed that sCO2 can effectively improve temperature uniformity along the heat sink in the presence of hotspots as compared to water. Considering a mass flow rate of 600 kg/(m2·s), the inhomogeneity index of the basal temperature of sCO2 is found to be 0.24, significantly lower than 4.22 for water. This indicates that sCO2 eliminates hot spots by rapidly increasing specific heat capacity near the pseudo-critical temperature. Furthermore, it is noted that maintaining the operating temperature of sCO2 near the pseudo-critical temperature can increase the specific heat capacity of the fluid in a short time, in addition to reducing the corresponding density and viscosity. Consequently, the entropy generation rate of sCO2 under ideal conditions is 46.6 % of that of water. Therefore, the proposed combination of a microchannel of complex structure and sCO2 in this study is demonstrated to effectively reduce the influence of hot spots and improve the overall thermal performance of heat sinks.