Water and energy are two of the most pressing problems faced by the world today. Membrane processes such as Reverse Osmosis (RO) and Pressure Retarded Osmosis (PRO) can help alleviate both challenges. This work focuses on systematic optimization of a RO-RO-PRO-PRO process for energy-efficient seawater desalination which integrates RO for desalination and PRO for power generation into a single process. Such a hybrid process is of great significance at the water-energy nexus given that water production, pump energy consumption, and hydraulic/osmotic energy recovery are inherently intertwined. The optimization problem is formulated to minimize the Specific Energy Consumption (SEC) subject to specified total membrane area and total water recovery. By solving the optimization model the best design (e.g., allocation of membrane area among different units) and operating (e.g. applied pressure in each membrane unit) conditions are simultaneously determined. It is shown that the proposed RO-RO-PRO-PRO allows a profile of the applied pressure that more closely tracks that of the concentrate osmotic pressure than RO-PRO, thus improving energy efficiency. Challenges and opportunities in further development of hybrid RO-PRO processes are discussed. (C) 2018 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.