Urban regeneration and local production of water, food, and energy are critical aspects of sustainable urban development. In the Italian context, there are many cities of former glory and with centralized development patterns, now struggling with aging infrastructure and deteriorating neighborhoods, looking for ways to optimize multiple energy and food sources. In this context, aquaponics, a sustainable farming method that combines aquaculture and hydroponics, could offer a solution to traditional urban farming methods, presenting opportunities for urban regeneration and local food production. In this context, two systems were considered: one of aquaponics and one of traditional cultivation, taking into consideration for this paper only water savings. Therefore, data from an aquaponic system were used, and Carbon Footprint (CF) and Water Footprint (WF) were considered, through the use of Simapro 9.5 software. The results show that through the use of aquaponic systems, to produce the same unit of production (1 kg of lettuce), it is possible to reduce water consumption by – 211 L and simultaneously reduce CF and WF by − 89%, as well as land use by − 84%. An interesting nexus could thus be established, as through aquaponic systems, food production could be increased and maximized (25 plants per m2 vs. 4 per m2), reducing the cultivation time (45 days vs. 25) and impacts, and thus, consequently increasing the amount harvested in a year (109.50 kg/m2 vs. 4.87 kg m2).