Pressure-retarded osmosis (PRO) is a promising technology that harvests salinity gradient energy. Even though PRO has great power-generating potential, its commercialization is currently facing many challenges. In this regard, this review highlights the discrepancies between the reported power density obtained by lab-scale PRO systems, as well as numerical investigations, and the significantly low power density values obtained by PRO pilot plants. This difference in performance is mainly due to the effect of a pressure drop and the draw pressure effect on the feed channel hydrodynamics, which have significant impacts on large-scale modules; however, it has a minor or no effect on small-scale ones. Therefore, this review outlines the underlying causes of the high power density values obtained by lab-scale PRO systems and numerical studies. Moreover, other challenges impeding PRO commercialization are discussed, including the effect of concentration polarization, the solution temperature, the pressure drop, and the draw pressure effect on the feed channel hydrodynamics. In conclusion, this review sheds valuable insights on the issues facing PRO commercialization and suggests recommendations that can facilitate the successful development of PRO power plants.