Menthol, a common additive in tobacco and electronic cigarette products, has been shown to interact with nicotine at both neuropharmacological and behavioral levels. Although menthol alone is not reinforcing, converging evidence indicates that it modulates the pharmacological and behavioral effects of nicotine via nicotinic acetylcholine receptor (nAChR)–dependent mechanisms. Using an inhalation-based rodent model that mimics human exposure to electronic nicotine delivery systems (ENDS), we examined the effects of menthol vapor on nicotine-induced hypothermia, discriminative stimulus effects, and the involvement of α4β2* nAChRs in male rats. Menthol vapor prolonged and potentiated nicotine-induced hypothermia, an effect that was attenuated by the α4β2* receptor antagonist dihydro-β-erythroidine (DHβE). In drug discrimination assays, co-administration of menthol enhanced nicotine-appropriate responding, indicating facilitation of nicotine’s interoceptive stimulus properties. These menthol-induced enhancements of nicotine’s subjective effects were blocked by DHβE, suggesting an essential role for α4β2* nAChRs in mediating the interaction between menthol and nicotine. These findings demonstrate that menthol modulates nicotine’s pharmacological and behavioral effects through α4β2* nAChR–dependent mechanisms. By enhancing receptor sensitivity and prolonging nicotine’s physiological effects, menthol may increase nicotine’s abuse liability when co-administered via inhalation. This study provides mechanistic insight into the neurobehavioral basis of menthol–nicotine interactions and underscores the importance of regulatory consideration for mentholated e-cigarette products.