This comprehensive review highlights the potential of sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, as a chemosensitizing agent in cancer treatment. SFN enhances the sensitivity of cancer cells to chemotherapy by modulating various signaling pathways and genes, thereby overcoming chemoresistance. The review covers the therapeutic potential of SFN across multiple cancer types, including bone, brain, breast, lung, skin, and others. Mechanistically, SFN affects pathways such as Akt/mTOR, NF-κB, and Wnt/β-catenin, and regulates proteins like p53, p21, survivin, Bcl-2, and caspases. When combined with conventional chemotherapeutic agents, SFN synergistically inhibits cancer cell proliferation, invasion, migration, and metastasis while potentiating drug-induced apoptosis. The review also discusses the ongoing preclinical and clinical investigations into the therapeutic potential of SFN, emphasizing its role in enhancing the efficacy of standard cancer treatments.This comprehensive review highlights the potential of sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, as a chemosensitizing agent in cancer treatment. SFN enhances the sensitivity of cancer cells to chemotherapy by modulating various signaling pathways and genes, thereby overcoming chemoresistance. The review covers the therapeutic potential of SFN across multiple cancer types, including bone, brain, breast, lung, skin, and others. Mechanistically, SFN affects pathways such as Akt/mTOR, NF-κB, and Wnt/β-catenin, and regulates proteins like p53, p21, survivin, Bcl-2, and caspases. When combined with conventional chemotherapeutic agents, SFN synergistically inhibits cancer cell proliferation, invasion, migration, and metastasis while potentiating drug-induced apoptosis. The review also discusses the ongoing preclinical and clinical investigations into the therapeutic potential of SFN, emphasizing its role in enhancing the efficacy of standard cancer treatments.