Mar Piccolo of Taranto is an estuarine basin heavily exploited for commercial mussel (Mytilus galloprovincialis L.) farming. The historical renown of the Taranto mussels has suffered over the last decade following policy decisions to expand the mussel farms and to relocate a portion of the urban sewage to an outfall outside of Mar Piccolo. The resulting decline in mussel quality and the quandary of how to restore stability to Taranto mussel production became the focal issue for our application of the systems approach framework (SAF). We simulated the ecological, economic, and social interactions that affect mussel production. Stakeholders and mussel farmers contributed by participating in meetings during the entire exercise. Our simulation analysis provided them with a means for understanding the effects of policy scenarios on the system. We present three aspects from our initial results that demonstrate the value of the SAF, as: (1) an operational model to monitor and better research the status of the ecosystem, (2) a management tool to evaluate sustainable mussel farming strategies, and (3) an opportunity for improved communication with and engagement of stakeholders, policy, and the public. The application has also raised important questions about how the food chain is controlled, what could be changed to stabilize the ecosystem to a higher level of productivity, and what role the public and policy could play in promoting sustainable development.