This study presents the mathematical formulation and implementation of a comprehensive optimization framework for the assessment of shale gas resources. The framework simultaneously integrates water management and the design and planning of the shale gas supply chain, from the shale formation to final product demand centers and from fresh water supply for hydraulic fracturing to water injection and/or disposal. The framework also addresses some issues regarding wastewater quality, i.e., total dissolved solids (TDS) concentration, as well as spatial and temporal variations in gas composition, features that typically arise in exploiting shale formations. In addition, the proposed framework also considers the integration of different modeling, simulation and optimization tools that are commonly used in the energy sector to evaluate the technical and economic viability of new energy sources. Finally, the capabilities of the proposed framework are illustrated through two case studies (A and B) involving 5 well-pads operating with constant and variable gas composition, respectively. The effects of the modeling of variable TDS concentration in the produced wastewater is also addressed in case study B. (C) 2016 Elsevier Ltd. All rights reserved.