For a study, researchers sought to analyze synovial sarcoma (SS) metabolism and determine how SS redox equilibrium is affected by malic enzyme 1 deficiency. Clinical SS tissues, SS cell lines, and tumors from an SS animal model were all examined for ME1 expression. Using Seahorse assays, metabolomics, and C13 tracings, the impact of ME1 deficiency on glucose metabolism was assessed. Measuring intracellular reactive oxygen species, cell death experiments using antioxidant system inhibitors, and metabolomics were all employed to assess the effects of ME1 depletion on SS reactive oxygen species (ROS). The ability of ME1-null SS to induce ferroptosis both in vitro and in vivo was tested. SS cell lines, an SS tumor model, and clinical samples were used to prove that SS does not contain ME1. ME1-null cells have been found to exhibit higher rates of glycolysis and a larger flow of glucose into the pentose phosphate pathway (PPP), which was required to make NADPH, according to studies on the SS’s glucose metabolism. An examination of cellular redox homeostasis reveals that the glutathione system was less sensitive to ME1 depletion than the thioredoxin system. Additionally, a lack of ME1 promotes the buildup of ROS and labile iron. ME1-null cells were more susceptible to the xCT  (erastin and ACXT-3102) inhibitor-induced ferroptosis due to ROS and iron buildup. ME1-null SS in vivo xenograft mice exhibits a much higher tumor response to ACXT-3102 than ME1-expressing controls. These results laid the preclinical groundwork for a phase I researched of ACXT-3102 in SS patients and showed the translational potential of targeting redox homeostasis in ME1-null cancers.