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Semiconductor devices and microelectronic devices are widely used in many applications such as central processing units. These devices produce a huge amount of heat that must be dissipated properly because their operation is sensitive to operating temperature. Under high operating temperatures, physical damage is expected because of thermal stresses harming the structure of the components and increasing the failure rate. The thermal management of these devices is mandatory to fulfill the recommended operating conditions. The complexity of applying even the most powerful single-phase liquid cooling arrangement is that the semiconductor component temperature increases linearly with increasing heat dissipation rate. Consequently, the temperature of the device could reach higher than the maximum temperature limit. Unlike the single-phase flow, the two-phase flow boiling–cooling system can provide more robust thermal management, uniform temperature distribution over the surface and high heat dissipation by the latent heat. Hence, the flow boiling in microscale devices is an effective cooling technique for high dense-power electronic components. The current study used ethanol, acetone, and Novec-7000 coolants with high, medium, and low boiling points, respectively to study the flow boiling in a microchannel device. The effects of the volumetric flow rate and heat flux were experimentally investigated. A graphite sheet was used as thermal interface material (TIM) for further enhancing the heat dissipation, and wall temperature uniformity was assessed under boiling conditions. The Novec-7000 coolant showed outstanding cooling capabilities under ultra-high-heat flux conditions. When TIM was used, effective heat flux increased by 0.62% and 1.62% for acetone and Novec-7000, respectively. Moreover, the experimental results showed that the boiling point is a critical parameter in the system performance of flow boiling–cooling.