Animal-source foods provide essential nutrients for humans, however, the use of nutrient-dense (i.e., high in nutrients but low in calories) and digestible resources for animal feeds is controversial as it may reduce the net contribution of farmed animals to global food supply, and hence to food security. Redirecting resources edible by humans to direct consumption as food can increase resource use efficiency and food supply, however, what can be considered as edible by humans is context dependent. The objective of the present study is to assess the net contribution of ten contrasting tilapia production systems from eight different countries to the supply of nutrients of importance for human health. To do so we calculated the human-edible nutrient conversion ratio (HeNCR), which is the human-edible nutrients in the inputs (feed) divided by the human-edible nutrients in the outputs (animal products) of the systems. We showed that tilapia systems can be net producers of proteins, but that in general, much more human edible micronutrients (5 to 175 times) and EPA + DHA (about 7 times) were in the feed used than in the fish produced. Four scenarios combining different definitions for feed and fish edibility were tested to explore the effect of different dietary changes on the performances of the tilapia systems. Scenario analysis revealed that the direct use of edible ingredients as food generates more nutrients than the consumption of fish. Consumers’ preferences, and therefore our definition of what is edible, may have to evolve in order to maximize food resource use.