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Many computational studies on hotspot microfluidic cooling devices found in the literature rely on simplified assumptions and conventions that do not capture the full complexity of the conjugate thermal problem. In this work it is analyzed the modeling of the overall heat transfer in a microfluidic device, focusing on the effect of the different thermal transfer mechanisms (conduction, convection and radiation), temperature-dependent thermophysical properties of the fluid, and the device material. The study is developed as a function of the pressure difference applied on the system based on simulations performed using a Finite Volume Method. Analyzing and comparing the contribution of the different factors to the energy losses, this work provides a critical discussion on the approximations usually considered, in order to perform a reliable modeling of the overall thermal performance of a real PDMS-based microfluidic heat sink.