Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps into solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor’s variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next generation sequencing has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the survival of patients with leukemia and solid tumors. The use of molecular diagnostics and the application of personalized targeted therapy in pediatric cancer can best be appreciated in relapsed/metastatic tumors, integrated morpho-molecular pathology diagnosis of new brain or hematologic malignancies, initial treatment of undifferentiated malignancies, and in the work-up of cancer predisposition syndromes. Novel techniques such as nanotechnology for precise drug delivery and immunotherapy with chimeric immunoreceptors promise a new direction and herald a bright future for more successful personalized targeted therapy. Although pediatric precision oncology is in its early phase, it has already affected the lives of many patients and provided grounds for more future practical developments.