Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype defined by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Limited actionable targets and frequent early relapse highlight the need for new therapeutic strategies. Here, we integrated patient-derived genome-scale metabolic modeling with CRISPR-Cas9 dependency datasets to identify TNBC-selective metabolic vulnerabilities. This analysis prioritized riboflavin kinase (RFK), an enzyme involved in FMN and FAD biosynthesis, as a candidate therapeutic target. Genetic depletion of RFK and pharmacological inhibition with roseoflavin suppressed TNBC cell growth in vitro and in orthotopic tumor models. Mechanistically, RFK suppression increased JNK phosphorylation while reducing ATF4 and SLC7A11 expression, leading to decreased glutathione availability, increased reactive oxygen species, lipid peroxidation, and impaired mitochondrial function. These changes induced ferroptotic and apoptotic cell death. Pharmacological modulation of JNK signaling further supported the role of the pJNK-ATF4-SLC7A11 axis in RFK-dependent redox regulation. Collectively, our findings identify RFK as a metabolic vulnerability in TNBC and suggest that RFK targeting may provide a therapeutic strategy by disrupting redox homeostasis and inducing ferroptosis and apoptosis.