Chemotherapy remains the cornerstone of cancer treatment, and has significantly improved patient survival. However, it is often accompanied by adverse effects that negatively impact quality of life, with neurotoxicity being one of the most debilitating yet often overlooked complications. This study aims to explore the influence of genetic variations on chemotherapy-induced neurotoxicity. Utilizing the PharmGKB database, we identified genetic variants associated with neurotoxic responses and assessed their Level of Evidence (LOE). Our findings highlight several genes, BCL2, OPRM1, SOX10, TRPV1, CYP3A4*22, GSK3β, DPYD, and ADORA2A, that are involved in neurotoxicity induced by chemotherapeutic agents, such as platinum/taxane, vincristine, fluorouracil, and methotrexate. These genetic factors modulate individual susceptibility to neurotoxic side effects. Understanding these associations supports the development of genotype-guided therapeutic strategies to reduce toxicity and improve quality of life in cancer patients receiving chemotherapy. 2026, Bentham Science Publishers