The joint culture of multiple species or even multiple life stages of the same species in the same system is a long-practiced method identified as co-culture or polyculture. Stocking several species with different food habits allows the effective exploitation of a variety of available foods in the ecosystem, thus improving economics and sustainability. Tilapia are omnivorous fishes grown in co-culture with a variety of other fish and crustacean species for production purposes, and/or environmental control, and/or with a predatory fish species to control tilapia recruitment in growout ponds. Tilapia co-culture is carried out in fishponds, rice fields, cages and pens within ponds, periphyton-based ponds, and partitioned and other intensive aquaculture systems. In all cases, pond ecology will largely be determined by the relationships among the different co-cultured species, the environment, and management decisions and procedures that are applied. The ecological basis governing the functioning of aquatic ecosystems applies to aquaculture systems. The components are primary producers, consumers, and decomposers, among which predator–prey and competition relationships determine nutrient and organic matter flows. Over this general pattern, the relationships between organisms and environment differ with the cultured species involved, and there are differences related to specific characteristics of each production system and its management. This chapter presents the role of tilapia in the pond ecosystem, ecological aspects of tilapia co-culture with fish and crustaceans in several production systems, tilapia co-culture as a management tool for environmental control, and tilapia co-culture with a predator to control tilapia recruitment. Examples of synergistic mutual effects through the food web and environment are described for tilapia co-culture with carp in ponds and in rice fields; tilapia co-culture with catfish in ponds; cage-cum-pond and partitioned systems; and tilapia co-culture with crustaceans in ponds; cage-cum-pond; and periphyton-based ponds. Conceptual graphic models of the ecosystem functioning for some of those co-cultures are presented.