The severity of symptoms and the need for intervention depend on the size of the defect and its physiological impact. Diagnosis typically involves advanced imaging techniques such as echocardiography, electrocardiograms, and cardiac catheterization, which are essential for accurate evaluation and management. Recent advancements in proteomics have significantly enhanced our understanding of congenital heart disease, offering detailed insights into cardiac development at the molecular level. Proteomic approaches help identify biomarkers, improve diagnostic accuracy, and facilitate the discovery of new therapeutic strategies. The insulin-like growth factor-2 (IGF-2) pathway plays a critical role in cardiac growth, development, and regeneration. This pathway influences processes such as cardiomyocyte proliferation and differentiation, making it a potential target for novel treatments aimed at repairing or regenerating damaged heart tissue. Objective: This review article aimed to throw the light on the relation between Insulin- like Growth Factor 2 and Ventricular Septal Defect in pediatrics. Materials and methods: We searched Google Scholar, Science Direct, PubMed and other online databases for VSD, IGF-2, Congenital heart defects and Pediatric cardiology. The authors also reviewed references from pertinent literature, however only the most recent or comprehensive studies from 1996 to 2021 were included. Documents in languages other than English were disqualified due to lack of translation-related sources. Papers such as unpublished manuscripts, oral presentations, conference abstracts, and dissertations that were not part of larger scientific studies were excluded. Conclusion: Integrating advanced diagnostic technologies with molecular and proteomic research provides a promising avenue for improving outcomes in congenital heart defects. These approaches not only enhance early detection and precise management but also open doors to innovative therapies for pediatric patients with complex cardiac conditions.