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Low-grade heat energy from resources below 100 °C is readily available in massive quantities worldwide. However, existing technologies face challenges in converting this heat power into usable forms of energy, such as electricity. This is primarily due to temperature fluctuations in these heat sources and the limited temperature gradient with the surrounding environment. To address this issue, a recently developed technology called thermo-osmotic energy conversion (TOEC) offers a promising solution for harvesting electrical energy from low-grade heat sources. In the TOEC method, a hydrophobic membrane facilitates the transfer of water vapor molecules from a moderately hot aqueous solution to a cold water stream. The resulting hydraulic pressure in the compressed water on the cold side can be harnessed using a hydro-turbine. Despite the many interesting features of TOEC technology, a comprehensive analysis of its performance under various operating conditions and membrane properties is currently lacking in the literature. In this study, we conducted a theoretical evaluation of the TOEC process based on mass and heat transfer phenomena, and we validated our findings with experimental data. Our results indicate that employing membranes with smaller pore size, low thickness, and high porosity, along with higher feed temperature and flowrates, can significantly enhance energy efficiency and power density. Specifically, we demonstrate that the utilization of hydrophobic membranes with nanometer-sized pores, coupled with hydraulic pressures ranging from 6.2 bar to 11.8 bar, enables us to achieve power densities exceeding 5 W/m2, given a 20 °C heat sink and a heat source temperature above 65 °C. Furthermore, we have determined that an applied hydraulic pressure of 9.4 bar yields the maximum energy efficiency value of 0.016%.