Abstract: Desalination is a critical separation process for combating global water stress. In this thesis synergistic desalination processes are developed using process synthesis, integration, and techno-economic optimization. Reverse osmosis (RO), accounts for 96% of desalinated water in the U.S. However, it is plagued by the problem of mineral scaling on membrane, which reduces the water recovery and increases the brine production. Novel hybrid RO desalination processes involving Ion Exchange (IEX) water softening and heating by direct injection of steam were developed and optimized. The IEX was regenerated with the concentrate from RO, eliminating the need for external regeneration chemicals. The hybrid processes developed at the scale of 1-96 million US gallons per day for concentrated brackish groundwater of southwest USA and for the Colorado River alleviated the problem of mineral scaling and improved the water recovery to as high as 96%. Annual savings amounting to US$ 15 million were estimated. Produced water is the largest volume byproduct stream in oil and gas production. USA produces about 7 barrel of produced water per barrel of oil. Produced water has an adverse environmental impact due to its complex composition and disposal costs can be as high as US$ 20/barrel. Critical to water recovery in the RO desalination of produced water is membrane fouling due to hydrocarbons. A novel hybrid Adsorption/IEX/RO process was developed for produced water purification. The adsorber removed the dissolved hydrocarbons while the IEX removed scale causing precursors. The adsorber was regenerated by a novel method. A part of the hydrocarbon free discharge from the adsorber is pressurized, heated to 160°C and then used to regenerate the adsorber. Improvement in water recovery (to 86%) translated into a predicted 22.8% decrease in costs amounting to US$ 27 million annual savings. The new high water recovery processes delineated in this work provide an array of novel options for desalination under different conditions. A generalized methodology for process synthesis, integration and optimization is presented.