A multi-objective structural optimization of integrated thermal desalination and thermal compression systems is performed, whereby the performance ratio of the structures is maximized while the specific area requirements are minimized. With the aid of the superstructure developed in part I, herein the thermal compression of vapor streams produced in intermediate multi-effect distillation (MED) effects as opposed to the common practice of compressing vapors produced in the last effect, is examined. The study concludes that intermediate vapor compression results in significant reductions in area requirements, as well as significant increases in maximum distillate production capacities. Moreover, the optimal location of vapor extraction is heavily dependent on the exact distillate production requirement in question. Two novel configuration forms are informed by the optimization. The first is an integrated MED-TVC + MED + MSF system, while the second is an integrated MED-TVC + MSF system. (C) 2014 The Authors. Published by Elsevier B.V.