In a zero-waste approach for the agro-industrial sector, this study aimed to evaluate the reuse of cheese whey wastewater (chemical oxygen demand = 2.1 g L−1) pretreated by immediate one-step lime precipitation followed by natural carbonation as a nutritive solution for tomato production in hydroponic systems. Pretreated effluent, diluted with groundwater (1:6) and supplemented with nutrients, was utilized to irrigate different hydroponic systems designed to assess the influence of tomato rooting type (free/confined−setup_A) and the feed’s solution level (with/without water deep−setup_B). Plants and fruit development, fruit physicochemical characteristics and sensory analysis, and effluent quality after reuse were analyzed. Good quality tomato production with high crop yield was obtained. The highest marketable tomato weight per plant (682 g) was observed in setup_B with a deep-bed system, but setup_A, with free or confined rooting, presented similar values. The type of rooting, within setup_A or water deep within setup_B, did not significantly influence plant and fruit characteristics. The highest maturity and flavor indexes were observed for setup_A with free rooting. Regarding sensory analysis, setup_A often scored the highest in terms of overall appreciation with free or confined rooting. The reuse of cheese whey wastewater in hydroponics reduced freshwater consumption for crop production, allowed for a treated final effluent and prevented soil degradation in a sustainable circular economy methodology.