The graphic processing unit is the active component that is an important heat source in electronic devices. The GPU cooling system's thermal dissipation performance with de-ionized water and nanofluid as coolants are presented. In the experiment, the GPU cooling system was embedded with the personal computer's GPU board, which in the overclock operating condition. The Ag nanofluid with 0.015% by volume concentration and de-ionized water is used as coolants flowing in the cooling system, considering the effects of coolant types and heat sink configurations on the thermal resistance. It found that the nanoparticles suspending in the base fluid significantly impact the nanofluid's physical properties and flow features, which results in higher removal capacity and, consequently, lower thermal resistance. The heat sink with a lower flow channel gives lower thermal resistance than those from higher ones. The results from this work have been used to develop a knowledge base that can be used to a design-related thermal cooling system for GPU or other components of electronic devices.