This review explores the chemosensitizing potential of sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, in enhancing the efficacy of cancer therapies. SFN has shown significant chemosensitizing effects across various cancer types, including bladder, brain, breast, colorectal, lung, ovarian, pancreatic, prostate, and skin cancers. It works by modulating multiple signaling pathways, such as Akt/mTOR, NF-κB, Wnt/β-catenin, and regulating key genes, proteins, and enzymes 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 promoting drug-induced apoptosis. SFN's chemosensitizing action is attributed to its ability to overcome chemoresistance by targeting various mechanisms, including the modulation of drug transport proteins, disruption of signaling pathways, and induction of apoptosis. It has been shown to enhance the effectiveness of other chemotherapeutic agents and phytochemicals in combination therapies. For instance, SFN combined with cisplatin, paclitaxel, and other agents has been found to reduce tumor growth, inhibit metastasis, and increase drug sensitivity in various cancer models. The review highlights SFN's potential as a chemosensitizer and a candidate for combination therapy in cancer treatment. It emphasizes the importance of understanding the molecular mechanisms underlying SFN's chemosensitizing effects to develop more effective therapeutic strategies. The study also discusses the role of SFN in modulating non-coding RNAs and its potential to enhance the therapeutic efficacy of anti-cancer agents. Overall, SFN shows promise as a complementary agent in cancer therapy, offering a new avenue for improving treatment outcomes and managing chemoresistance.This review explores the chemosensitizing potential of sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, in enhancing the efficacy of cancer therapies. SFN has shown significant chemosensitizing effects across various cancer types, including bladder, brain, breast, colorectal, lung, ovarian, pancreatic, prostate, and skin cancers. It works by modulating multiple signaling pathways, such as Akt/mTOR, NF-κB, Wnt/β-catenin, and regulating key genes, proteins, and enzymes 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 promoting drug-induced apoptosis. SFN's chemosensitizing action is attributed to its ability to overcome chemoresistance by targeting various mechanisms, including the modulation of drug transport proteins, disruption of signaling pathways, and induction of apoptosis. It has been shown to enhance the effectiveness of other chemotherapeutic agents and phytochemicals in combination therapies. For instance, SFN combined with cisplatin, paclitaxel, and other agents has been found to reduce tumor growth, inhibit metastasis, and increase drug sensitivity in various cancer models. The review highlights SFN's potential as a chemosensitizer and a candidate for combination therapy in cancer treatment. It emphasizes the importance of understanding the molecular mechanisms underlying SFN's chemosensitizing effects to develop more effective therapeutic strategies. The study also discusses the role of SFN in modulating non-coding RNAs and its potential to enhance the therapeutic efficacy of anti-cancer agents. Overall, SFN shows promise as a complementary agent in cancer therapy, offering a new avenue for improving treatment outcomes and managing chemoresistance.