Cenobamate (CNB) demonstrates high efficacy in drug-resistant focal epilepsy, yet optimal management requires personalized strategies. This exploratory case series describes five patients selected from a cohort of 125 individuals treated with CNB, examining the relationship between pharmacogenetic (PGx) profiles and clinical outcomes. Clinical data and therapeutic drug monitoring (TDM) were integrated with targeted Next-Generation Sequencing of key metabolic genes (UGT2B7, UGT2B4, CYP2E1, CYP2B6