Pressure retarded osmosis (PRO) is a technology that could be utilized to recover energy from the mixing of freshwater with seawater. This source of renewable energy is sizeable and in the past decade several investigations analyzed its potential. The vast majority of studies focused on mass transfer problems across the membrane in order to improve membrane productivity and just recently studies started to look at membrane module efficiencies and parasitic loads within the PRO facility. In this article, the net specific energy production from a facility-scale PRO system was determined and optimized by using a novel simulation method that integrates parasitic loads and efficiencies of the PRO facility components and combines the model with an optimization software in a linked system optimization scheme. It was found that the overall net specific energy that may be recovered by a river-to-sea PRO facility is approximately 0.12 kWh per m3 of permeate. Furthermore, a sensitivity analysis was performed to elucidate the relationship between net specific energy and power density as functions of membrane area, flow rates, and operating pressures. In general, in order to maximize resource recovery, a low power density, thus a low membrane productivity, must be accepted.