Designing effective wastewater treatment networks is challenging because of the large number of treatment options available for performing similar tasks. Each treatment option has variability in cost and contaminant removal efficiency. Moreover, their mathematical models are highly nonlinear, thus rendering them computationally intensive. Such systems yield mixed-integer nonlinear programming models which cannot be solved properly with contemporary optimization tools that may result in local optima or may fail to converge. Herein, the P-graph framework is employed, thus generating all potentially feasible process structures, which results in simpler, smaller mathematical models. All potentially feasible process networks are evaluated by nonlinear programming resulting in guaranteed global optimum; furthermore, the ranked list of the n-best networks is also available. With the proposed tool, better facilities can be designed handling complex waste streams with minimal cost and reasonable environmental impact. The novel method is illustrated with two case studies showing its computational effectiveness.