The rise in world population and industrialization in developing nations has tremendously increased the demand for water and has resulted in wastewater contaminated with several pollutants. Thus, wastewater treatment (WWT), reuse, and safe disposal have become crucial for sustainable existence. We believe that generation of a maximal structure (superstructure) comprising of all possible treatment methods and flow patterns using a systems approach, followed by optimization to decide the best treatment pathway, will enable efficient designing of WWT networks. In this work, the technologies/methods involved in WWT such as sedimentation, filtration, membranes, adsorption, activated sludge, etc. are modelled using material and energy balances, equipment design, costing and environmental impact. Utilizing systematic methods (e.g. mixed-integer non-linear programming, MINLP), we frame the WWT network selection as an optimization problem for cost and energy minimization along with sustainable goals. In our analysis, we demonstrate a case study of Municipal WWT and determine the best strategy in compliance with the 1972 US EPA's Clean Water Act to reuse the treated water for cropland irrigation. In the next step, we use the P-graph approach for solving the same problem and this tool provides a ranked list of candidate solutions.