Context: Palliative sedation therapy (PST) can address suffering at the end of life (EOL) in children with cancer; yet, little is known about PST in this population. Objectives: We sought to describe the characteristics of pediatric oncology patients requiring PST at the EOL. Methods: A retrospective review was completed for pediatric oncology patients who required PST at a United States academic institution over 10 years, including demographics, disease characteristics, EOL characteristics, and medications for PST and symptom management. Results: PST was utilized in 3% of patients at the EOL. Of 24 study participants receiving PST, 83% (n = 20), 12.5% (n = 3), and 4.2% (n = 1) received dexmedetomidine, propofol, or both, respectively. The most frequent diagnosis for patients receiving PST was acute myelogenous leukemia (20.8%, n = 5). All patients were followed up by the palliative care team, and two-thirds (66.6%, n = 16) were also followed up by the pain management service; 79% (n = 19) were enrolled in hospice, and 98.5% (n = 23) had a Physician Orders for Scope of Treatment in place. Pain was the most common refractory symptom leading to PST initiation (33.3%, n = 8), followed by neuroagitation and dyspnea. PST was initiated a median of 2.5 days before death. A third of deaths occurred in the intensive care unit (33.3%, n = 8). Conclusions: PST was rare in this study; dexmedetomidine was used as first-line treatment for PST in patients at the EOL with refractory symptoms. Its place in PST protocols in pediatric oncology should be validated with prospective studies. Our study suggests the potential value of collaboration between palliative care and pain specialists in the context of PST.