This study aims to systematically evaluate the detrimental effects, namely concentration polarization (CP) and reverse solute permeation (RSP), and search for the optimum performance of a scale-up osmotic power assisted reverse osmosis (RO) desalination plant. The simulation clearly shows the performance reductions of the hybrid RO-PRO plant due to the CP and RSP effects. However, in both the co-current and counter-current PRO configurations, when the overall dimensionless flow rate decreases, these performance reductions become less significant. In addition, the counter-current PRO has high effectiveness because of the low theoretical net specific energy consumption (SEC) of RO-PRO. It is observed that more severe reduction due to the CP and RSP effects at high overall dimensionless flow rate shrinks the advantageous performance. Furthermore, PRO feed solutions with different concentrations are studied to evaluate the overall performance of the hybrid system. The results indicate that the advantageous performance can be achieved in a range of the concentration of the PRO feed. And with the increase on the PRO feed concentration, the osmotic energy generation reduces but the un-extracted energy due to the detrimental effects is also reduced.