Inadequate production practices are widely used in aquaculture management, causing excessive water and energy usage, as well as ecological damage. New approaches to sustainable aquaculture attempt to increase production efficiency, while reducing the quantities generated of wastewater and sludge. The sustainable operating techniques are often ineffective, expensive, and difficult to implement. The present article proposes a zero-waste production system, designed for growing fish and vegetables, using a new circular operational concept that creates synergies between fish farming and horticulture. In order to optimize the operational flows with resources, products, and wastes in an integrated zero-waste food production cluster, a business model was designed associating three ecological production practices: a closed fishing pond, a technology for growing vegetables in straw bales, and a composting system. The design had the role to assist the transition toward multiple circular material flows, where the waste can be fully reintegrated into the production processes. A comparative evaluation was conducted in three alternative growing environments, namely, a soilless culture established in straw bales, a culture grown in soil that had received compost fertilizer, and the conventional farming technique. When compared to conventional methods, experiments showed a significant increase in the cluster’s cumulative productivity, resulting in a 12% improvement in energy efficiency, 18% increase in food production, and 25% decrease in operating expenses.