The impact of climate change, particularly drought, places an enormous pressure on the synthesis of process systems that use freshwater resources efficiently. This paper presents the synthesis of water-based polygeneration system to minimize freshwater consumption. A comprehensive model is formulated through a superstructure, featuring the possible configurations of simultaneous heat and power generations, re-circulating cooling water system, wastewater treatment options, as well as reaction and separation technologies for chemical production. Process units are modeled using Aspen Hysys 2006. A case study on the synthesis of optimum water polygeneration system is developed for an ethylene glycol production. The superstructure model is a mixed integer non-linear programming problem (MINLP) consisting of 305 equations, 326 variables and 20 binary variables. The objective of the model is to minimize freshwater make-up subject to 85 constraints. The model is subsequently solved using DICOPT++ in GAMS 20.7 with the optimum solution showing nearly 50 savings of freshwater consumption. © 2012 Elsevier B.V.