BACKGROUND: Head and neck cancer (HNC) encompasses a heterogeneous group of malignancies originating in the oral cavity, pharynx, nasopharynx, larynx, paranasal sinuses, and salivary glands. Accumulating evidence indicates that metabolic syndrome (MetS) characterized by a constellation of conditions including central adiposity, hyperglycemia, dyslipidemia, hypertension, and insulin resistance, may significantly influence cancer pathogenesis and progression. RESULTS: MetS has been epidemiologically linked to elevated risk for multiple malignancies through various metabolic mechanisms involving chronic systemic inflammation, insulin resistance, and dysregulated lipid metabolism. Especially in HNC, recent studies demonstrated that MetS and metabolic imbalance conditions may contribute to carcinogenesis, disease progression, and clinical outcomes, but the exact mechanisms behind the association between excess fat accumulation and HNC risk remain unclear. Considering previous studies, pharmacological agents targeting metabolic pathways, including biguanides (metformin), thiazolidinediones, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and HMG-CoA reductase inhibitors (statins) are being investigated for potential repurposing in cancer prevention and adjuvant therapy. CONCLUSIONS: Here, we summarize the latest evidence on the relationship between MetS and HNC, highlighting the therapeutic potential of anti-diabetes drugs and anti-dyslipidemia drugs in ameliorating various pathological problems in HNC patients with MetS.