The wastewater generated in urban areas is one of the main sources of water pollution, particularly in regions characterized with large population density and high urbanization degree. In this paper, we present an optimization model for regional wastewater systems planning. The model is aimed at helping to determine the best possible configuration (layout of sewer networks, location of treatment plants, etc.) for the wastewater system of a region taking economic, environmental, and technical criteria explicitly into account. It can be used separately, or as a building block of a broad decision-support tool designed to cover all (or most of) the issues involved in the implementation of an Integrated Water Resources Management approach. The model is solved through a simulated annealing algorithm. The type of results that can be obtained through the application of the model is illustrated for three case studies.