The osmotic pressure difference between river water and seawater is a promising source of renewable energy. However, current osmotic energy conversion processes show limited power output, mainly owing to the low performance of commercial ion-exchange membranes. Nanofluidic channels with tailored ion transport dynamics enable high-performance reverse electrodialysis to efficiently harvest renewable osmotic energy. In this Review, we discuss ion diffusion through nanofluidic channels and investigate the rational design and optimization of advanced membrane architectures. We highlight how the structure and charge distribution can be tailored to minimize resistance and promote energy conversion, and examine the possibility of integrating nanofluidic osmotic energy conversion with other technologies, such as desalination and water splitting. Finally, we give an outlook to future applications and discuss challenges that need to be overcome to enable large-scale, real-world applications.