Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune disorder characterized by brain and spinal cord inflammation. In pediatric patients, ADEM presents unique challenges due to its potential for rapid progression and long-term neurological sequelae. Therapeutic plasma exchange (TPE) has emerged as a potential treatment option by targeting the underlying autoimmune process and modulating the inflammatory response. This comprehensive review evaluates the role of TPE in pediatric ADEM, synthesizing evidence from clinical studies and providing insights into its efficacy, safety, and potential benefits. The review highlights the variability in TPE efficacy based on disease severity and patient-specific factors. Implications for clinical practice include considering TPE as a therapeutic option, particularly in severe or refractory cases, and emphasizing the importance of early intervention. Recommendations for future research include long-term prospective studies, comparative effectiveness trials, and efforts to standardize TPE protocols. Overall, continued investigation and innovation in managing pediatric ADEM are essential for improving outcomes and quality of life for affected children and their families.