Membrane science and technology has nowadays become the dominant technology in water desalination. In this context, Reverse Osmosis, in combination with other pressure-driven membrane operations (i.e., microfiltration, ultrafiltration and nanofiltration), represents the most diffuse practice. Despite this success, specific actions are requested in order to solve problems related to water recovery factors, brine disposal, cost and quality of the water. In this paper, a MF-NF-RO membrane system is integrated with membrane distillation/crystallization units. The use of these membrane contactors devices, operated on the NF and/or RO retentate, pen-nits to increase the water recovery factor up to 92.8% without a significant increase of the costs if waste thermal energy is already available to the process. In addition, the sale of salt crystals grown in high concentrated brines might potentially reduce the overall desalination cost, thus confirming the potential interest for the proposed approach. Energy and exergy analysis permitted to individuate the points of higher entropic losses and low thermodynamic efficiency for the systems, and possible solutions based on the use of energy recovery devices have been discussed in detail.