In this study, an initial pool of 8 compounds that have previously demonstrated feasibility in enhancing plant yield was finalized using a decision tree. These 8 compounds included Potato Starch (Starch), Sucrose, Humic Acid (HA), Citric Acid (CA), Ethylenediaminetetraacetic Acid Iron (III) (EDTA-Fe), Adenine, 6-Benzylaminopurine (6-BAP), and Seaweed Extract (SWE). Subsequently, WisDM Green assessed their interactions in red spinach that were grown with liquid fertilizers (Starxgrow) to pinpoint unique compound interactions that may lead to improved yield. WisDM Green harnessed prospectively obtained biological yield, or dry weight, data of red spinach grown in a set of compoundcombinations and subsequently, formulated a ranked list of optimal combinations based on percent yield (%Yield), which is the percentage difference in biological yield between treated and control plants. The streamlined workflow to determine compound combinations is outlined in Figure 2. Notably, 6-BAP/EDTA-Fe and HA/SWE combinations were able to achieve 26.34±15.80 and 33.59±14.60 increases in %Yield, respectively. Further interaction analysis suggested that compound combinations may have concentration-dependent interactions. Specifically, HA/SWE at concentrations 2 g L-1 and 12.5% v/v, respectively, resulted in 33.59±14.60 increase in %Yield; however, adjusting the concentration ratio to 0.25 g L-1 and 100% v/v, respectively, HA/SWE resulted in 9.36±14.42 decrease in %Yield. Concentration-dependent synergies observed in this study suggest that WisDM Green-pinpointed combinations containing lower or higher concentrations of specific compounds may potentially improve yield outcomes compared to traditional titration or high concentration approaches. Moreover, the nutrition profiles of red spinach grown with WisDM Green-pinpointed compound combinations had no statistically significant difference when compared to red spinach grown under control conditions, suggesting that improved %Yield may be achieved without compromising nutritional values. In this study, WisDM Green served as a proof-of-concept platform towards sustainable combinatorial design of growth compounds to increase plant yield without fertilizer-driven enhancement. This platform may also be broadly applicable towards other classes of agricultural products. However, further refinement of the platform will need to be considered in order for potential translation into a scalable agricultural workflow.