Pollution prevention and waste reduction efforts at pharmaceutical sites with ever-changing production campaigns require a dynamic model of the corporate business and manufacturing activities. Flexibility in business strategies for addressing evolving market demands or changes in environmental legislation add uncertainty to this already challenging design problem. In this third part of the triple series on plant-wide waste management, we extend the combinatorial process synthesis methodology to the computer-aided synthesis of long-term site-management strategies under uncertainty. The proposed framework formulates optimal management of operations and facilities as a multiperiod optimization problem with a planning horizon of typically 5 years. Our approach synthesizes a network of process operations to recover useful raw materials and solvents, treat unavoidable effluent streams to compliance, and suggest optimal capacity and timing of investment decisions for new facilities or process technology. In addition, the expected environmental discharges and emissions are projected for the entire planning horizon. The mathematical modeling and solution approach allows decision makers to assess the monetary, infrastructural, and ecological impact of new environmental legislation or changing production requirements on their businesses in advance. The methodology is validated with an industrial-type case study.