Evidence suggests a potential link between metabolic dysfunction and head and neck cancer (HNC). This study investigates the potential causal relationships between metabolic dysfunction and HNC using genetic data. While no significant causal associations were identified between metabolic indicators and HNC risk, the research revealed that inhibition of certain genes could reduce cancer risk. Specifically, inhibiting SLC5A2 was associated with a decreased risk of HNC and oropharyngeal cancer (OPC), while KCNJ11 inhibition was linked to a reduced risk of oral cavity cancer (OCC). Additionally, inhibiting SLC5A1 and CACNB2 showed a connection to lower OPC risk. These findings suggest that targeting these genes could offer promising therapeutic strategies for preventing and treating HNC, as well as improving both preoperative and postoperative management in affected patients.