Precision medicine is a developing strategy for individualized treatment of a wide range of diseases. Congenital heart disease is the most common of all congenital defects and carries a high degree of variability in outcomes because of unidentified causes. Advances have identified individual genetic and environmental factors that have helped understand variations in morbidity and mortality in pediatric cardiology. A focus on genomics and pharmacogenetics has also been key to risk prediction and improvement in drug safety and efficacy in the pediatric population. With the rapidly evolving understanding of these individual factors, there also come challenges in implementation of personalized medicine into our health care model. This review outlines the key features of precision medicine in pediatric cardiology and highlights the clinical effects of these findings in patients with congenital heart disease. [Pediatr Ann. 2022;51(10):e390-e395.].