Background: The chronic autoimmune condition, pediatric vitiligo, causes depigmentation, which leads to severe psychological distress during important developmental periods. The emerging therapies JAK inhibitors and oral compound glycyrrhizin address the immune-mediated melanocyte destruction in pediatric vitiligo patients, but they do not address the substantial psychosocial challenges these children face. This review examines the clinical effectiveness and psychosocial results of combined treatments for pediatric vitiligo while focusing on cultural elements and new gene-directed therapeutic approaches.

Methods: A systematic literature search was conducted across PubMed, Embase, PsycINFO, Web of Science, and Cochrane Library in May 2025 using terms related to pediatric vitiligo, clinical and psychosocial interventions, suicide risk, and molecular therapies. Eligible peer-reviewed studies (2010–2025) included children aged 0–18 with vitiligo and evaluated repigmentation outcomes, mental health impacts, or integrated treatment approaches. Studies were screened and reviewed by five independent reviewers. Risk of bias was assessed using Cochrane and ROBINS-I tools, and evidence strength was evaluated with GRADE.

Results: Our review demonstrated that topical JAK inhibitors together with glycyrrhizin-phototherapy combinations and prostaglandin analogues and Wnt/β-catenin signaling agonists proved effective for repigmentation with good safety results in children. There is an urgent need for randomized trials to evaluate the combination of medical and psychosocial interventions. The combination of psychological stress and stigma particularly affected children of color because it led to decreased quality of life and elevated their chances of developing depression, anxiety, and suicidal tendencies. The combination of family-based therapy with cognitive behavioral therapy (CBT) and culturally adapted interventions demonstrated effectiveness in strengthening emotional resilience and improving treatment adherence. The experimental phase of pediatric research includes gene-editing technologies (e.g., CRISPR), mRNA-based therapies, and melanocyte transplantation.

Conclusion: Pediatric vitiligo management must evolve toward an integrated model that addresses both biological and psychosocial dimensions of care. Existing therapies offer promising repigmentation outcomes, but their full potential is limited without concurrent psychological support. Longitudinal, multicenter trials measuring both clinical and psychosocial endpoints, particularly in diverse pediatric populations, are urgently needed. Additionally, culturally sensitive interventions and gene-based strategies may shape the future of personalized vitiligo care.