With the growing consumer demand in the electronics field, sustainable and effective cooling approaches are imperative to maximize operational efficiency. Heat pipes shave a major consideration in the field of heat transfer in a modern era of miniaturization of equipment. In current trends, the proportion of custom-designed electronic chips is increasing, given the space constraints of the application. Additionally, the use of nanofluids in heat pipes has drawn considerable attention because of their exceptional performance in heat transfer. This research is proposed primarily to investigate the effect of nanofluids on the performance of the partially flattened heat pipe. Here, the evaporator portion forms flat shape which is mostly suitable for fixing easily in electronic circuits. The remaining portions, such as the adiabatic and condenser, are left as circular. This work also covers the development of flattened heat pipes and analyzes their performance. Pure water, Titanium Oxide (TiO2), and Aluminum Oxide (Al2O3)-water-based nanofluids have been used in this research as working fluids. The heat transfer analysis on the customized partially flattened heat pipe was performed, and the results have been compared with fully flattened and circular heat pipes. The heat transfer parameters, such as the heat transfer coefficient and thermal resistance, have been determined from the heat input, evaporator temperature, and condenser temperature for various inclination angles including 0°, 45°, and 90° with the heat input varied between 50–300 W. The results have shown that the flattened heat pipe performed better with Al2O3 nanofluid at an inclination angle of 45° at all of the heat inputs and provided better thermal resistance compared with the other combinations. At 45°, the resistance of the heat pipe was reduced by 2% and 8% with Al2O3 nanofluid compared with water and TiO2 nanofluid. Furthermore, the heat transfer coefficient was found higher by 4 W/m2-K and 4.6 W/m2-K with Al2O3 and gives better results in terms of resistance and heat transfer coefficient.