Objective Procedural sedation and analgesia are the standard of care for painful procedures in children that require immobility. The aim is to assess the safety and efficacy of procedural sedation and analgesia in pediatric oncological patients in a large tertiary care hospital. Method An observational study performed to review medical records of children who received procedural sedation and analgesia (PSA) for pediatric oncological procedures from July 2018 to September 2018. Patients undergoing oncology procedures (lumbar puncture, intrathecal chemotherapy, bone marrow aspiration +/- trephine) were included, and non-anesthesiologist (intensive care physician/emergency physician certified in pediatric advanced life support) provided PSA. Patients were assessed according to PSA protocol guidelines by the American Society of Anesthesiology (ASA). Low-dose ketamine (0.5 mg/kg) and propofol (2 mg/kg) were administered. Results A total of 565 children underwent 1216 procedures in whom the median age was 7.4 years, and the majority (65.1%) were males. The most common procedure was the lumbar puncture (n = 956; 78.6%) followed by bone marrow aspirate only (n = 137, 11.3%) and both (n = 123, 10.1%). Eight (0.7%) patients developed transient oxygen desaturation only as an adverse effect of ketamine-propofol drug combination with 50% procedures utilizing propofol 1 mg/kg for sedation. Conclusion According to the results of our study, the majority of the pediatric patients responded and reported no adverse events during the procedure with ketamine and propofol. Therefore, we conclude that ketamine and propofol are safe and effective as both sedative and an analgesic in procedures on pediatric oncology patients.