Epilepsy imposes substantial challenges on informal caregivers, who play a vital role in supporting individuals with this condition. This review aims to explore the burden experienced by informal caregivers of adults with epilepsy and identify critical factors that influence their overall experience. A literature review was conducted following PRISMA guidelines. PubMed and ScienceDirect were searched for identifying original research articles published in English from January 2005 till the end of February 2024. Studies were critically appraised using the AXIS Critical Appraisal Tool for Cross-Sectional Studies. Data were extracted and a narrative synthesis was performed. Twelve studies involving 1.265 participants were included. Eight studies were rated as high quality, while four were rated as fair quality. Six primary determinants of caregiver burden were identified: care-recipient characteristics, caregiver characteristics, psychological and physical factors, availability of support system, ethnicity and culture, and stigma. The majority of studies reported mild-to-moderate levels of caregiver burden, reflecting the diverse challenges faced by caregivers providing assistance to adults with epilepsy. While this review identifies several factors influencing caregiver burden, prospective longitudinal and qualitative studies are essential to unravel the multidimensional nature of caregiver burden and its variations across diverse cultural settings.