The thermal performance of a plate fin heat sink was investigated as a function of the location of multiple heat sources to minimize the thermal interference effect. Numerical analysis was performed under forced-convection conditions to design a cooling system for a high-power heat source. The thermal behaviors of the heat sink and surrounding air were simulated. We also investigated the thermal performances of various base thicknesses under local heat flux conditions to determine the optimal heat sink base thickness using the width of the heat source and conduction coefficient of the heat sink. The optimal location was determined by investigating the effects of the Reynolds number, thermal conductivity of the heat sink, heat transfer rate ratio for multiple heat sources, and width of the heat source. An installation guideline of the plate fin heat sink was prepared to help users avoid the thermal interference effect depending on the width of their heat source. By applying a correlation equation to obtain the optimal location where the maximal temperature of the heat source is minimized, the thermal resistance was decreased by up to 30%.