Background and Objective: Epilepsy is a common neurological condition that significantly impacts quality of life, particularly in cases of drug-resistant epilepsy (DRE). Perampanel, a third-generation antiseizure medication (ASM), has shown promise as a treatment option. This case report describes the successful long-term management of a patient with DRE using perampanel after deferring epilepsy surgery. Materials and Methods: A 49-year-old woman with a history of multiple medical comorbidities, including morbid obesity, experienced drug-resistant focal to bilateral tonic clonic seizures since age 40. She had failed trials of various ASMs. Intracranial Electroencephalogram (iEEG) monitoring confirmed a left temporal lobe epileptic focus but the surgical intervention was deferred due to her complex medical status. Perampanel was subsequently added to her treatment regimen and the patient achieved sustained seizure remission for over 5 years. Results: This case highlights the potential utility of perampanel in the management of DRE, particularly in patients unsuitable for or deferring epilepsy surgery. The long-term seizure freedom achieved with perampanel in this complex case suggests it may serve as a valuable alternative therapeutic option. Conclusion: Further research is warranted to elucidate the role of perampanel in the comprehensive care of individuals with DRE.