The authors have developed operating strategies for energy cost minimization and effluent regulation of an interconnected system of advanced wastewater treatment plants in Hillsborough County, FL. Inner-loop optimization has been performed on individual plant-wide transient operation of energy-intensive processes, while outer-loop optimization has been designed for influent and process stream manipulation and transmission between sites via plant-to-plant interconnects, transfer pumps, and lift stations. Forecasting models have been generated using artificial neural networks for inter-plant operability, and rules have been generated for supervisory decision making.