In regions with intensive agricultural production, large amounts of organic waste are produced by livestock animals. Liquid digestate from manure-based biogas production could potentially serve as fertilizer if integrated with closed horticultural irrigation systems. The aim of this experiment was to investigate how fertilizer based on liquid biogas by-products of pig manure digestion can affect the growth and production of tomato plants. Integration of a nitrification bioreactor presumes a significantly lower concentration of nutrient solutions and a higher level of oxygenation than classical mineral cultivation. Therefore, additional controls were included. We compared plant growth and fruit quality traits of tomato plants grown in a hydroponic solution with organic fertilizer with two levels of mineral fertilizer. The tomatoes grown with organic waste-based liquid fertilizer showed reduced growth rates but increased mean fruit size, resulting in no significant change in total yield compared with high-mineral cultivation. The growth rate was similarly reduced in plants cultivated with low-mineral fertilizer. Plants cultivated with organic waste-based fertilizer had high Cl⁻ concentration in xylem sap, leaves, and, ultimately, fruits. The leaves of plants cultivated with organic waste-based fertilizer contained higher concentrations of starch and soluble carbohydrate and low concentrations of phosphorous (P) and sulfur (S). The plants grown with organic waste-based or low-mineral medium showed significantly poorer fruit quality than the plants cultivated with the high-mineral solution. The low-mineral treatment increased xylem sap contribution to fruit weight because of higher root power. The organic waste-based fertilization did not change the root power but increased fruit size. In conclusion, organic waste-based cultivation is a possible solution for sustainable plant production in greenhouses. However, additional adjustment of nutrient supply is required to improve fruit quality.