Motivated by the need for environmentally friendly energy-generating devices toward sustainable development and a secure energy future for the planet, the current work investigates high energy-density-producing devices utilizing the nanofluidic reverse electrodialysis approach, considering salinity gradients and pH influences in the ionic transport. Non-uniformly charged nanochannels have been considered to achieve the desired goal. This choice is expected to facilitate the regulation of the ionic field. The negative-positive-negative (NPN) and positive-negative-positive (PNP) surface-charged nanochannels are considered to be the non-uniform charged configurations. By altering the pH of the right-side reservoir (pHright) in comparison to the corresponding uniformly charged designs having positively charged walls and negatively charged walls, it was possible to compare the corresponding ionic and fluidic characteristics. By altering the pHright value, it becomes evident that the nanoslit’s unevenly charged surface can substantially affect the potential field and its gradient locally. The competition between cationic and anionic currents enables a highly cationic selective PNP nanoslit for the extremely acidic right reservoir. In contrast, the NPN nanoslit allows for greater anionic selectivity in the highly basic right reservoir. In addition, the PNP case achieves maximum electrical conductance, enabling a larger maximum generated power in the lower pHright range. Whereas, for the highly basic solution, electrical conductance as well as generated power were found to be higher for the NPN configuration. Remarkably, power density in the PNP and NPN configurations exceeds the commercial threshold limit in highly acidic and basic pHright values, respectively. We showed that the non-uniformly charged designs have higher average flow velocity or mass flow rate for almost every pHright (except close to pHright 4 and 10) under the salinity gradient. As such, information from this work can contribute to the development of more efficient nanofluidic devices that control flow and generate greater power density and flow rates.