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Pediatric hematology-oncology can be challenging for the palliative care advanced practice registered nurse (APRN). The palliative APRN must appreciate that children with a cancer or blood disease often suffer from a multitude of symptoms which threaten the intactness and quality of life of the child and family. Early integration of palliative care may mitigate suffering and fosters improved coping throughout the trajectory of the underlying disease. Specifically, the initiation of therapies with curative intent concurrently with those that ease suffering can promote quality of life and well-being. Due to the complexity of symptom management, essential crucial conversations, and the therapies’ impact on quality of life, the presence of a palliative APRN for these patients is vital.