In this research, 3-D numerical analysis is carried out for single-phase laminar flow in a minichannel heat sink subjected to a uniform value of heat flux. The influence of various substrate materials (Aluminum nitride AlN, Copper alloy Cu, and Silicon Si) and different working fluids GaIn, GaIn-based nanofluids (GaIn-6 %CNT, GaIn-6 %Diamond, GaIn-6 %Alumina) and water on the maximum heat flux, pumping power, average heat transfer coefficient, total thermal resistance and pressure loss is examined for Reynolds number (Re = 300 - 1900) inside minichannel. It is noted that the substrate's conductivity substantially influences the heat transfer coefficient of minichannel, with higher conductivity leading to a higher heat transfer coefficient. Besides, among all the coolants, the GaIn-6 %CNT alloy with superior thermal conductivity shows an enhanced heat transfer coefficient compared to other coolants in this study. Simulations results depict that the average heat transfer coefficient (h) of GaIn-6 %CNT, GaIn-6 %Diam, and GaIn-6 %Al2O3 relative to that of GaIn alloy is increased by 8.40 %, 7.63 %, and 0.22 %, respectively for Cu substrate at phi = 6 % and Re = 1900. Moreover, for GaIn-6 %CNT, which is used as a liquid metal nanofluid, and Cu is replaced with Si substrate, (h) increases by 35 % and 62.5 % at Re = 1900 and Re = 300, respectively. Similarly, when Cu is used to replace AlN, (h) increases by 11 % and 18.20 % for Re = 1900 and Re = 300, respectively. Finally, numerical findings of the pressure loss and pumping power for working fluids employed in minichannel are discussed and compared with the calculations obtained by analytical correlations.