A large body of published clinical research supports the effectiveness of leading Pediatric IO modalities, while addressing potential safety-related concerns. Despite the growing amount of clinical research supporting the beneficial effects and implementation of Pediatric IO models of care, there is still a need for further studies in order to establish clinical guidelines in the treatment of children and adolescents with cancer. Such IO-directed guidelines will need to address both the effectiveness and the safety of the CAM modalities being used in pediatric oncology and hemato-oncology settings, promoting a better understanding among pediatric healthcare professionals and helping them understand the indications for referral to the IO treatment service.