Objective: Virtual Reality (VR), a novel and highly immersive technology, offers promise in addressing potential psychological impacts of cancer treatments and hospitalization. The primary aim of this study was to examine multiple key user perspectives on the acceptability and feasibility of an Immersive VR therapeutic intervention for use with hospitalized oncology patients. Secondary aims were to identify issues and opportunities related to the adoption and clinical implementation of VR in pediatric oncology settings. Methods: The study was conducted at the Royal Children’s Hospital, Melbourne, Australia. Thirty multidisciplinary oncology healthcare professionals (HCPs) participated in an initial test of VR intervention usability (Stage 1). Ninety oncology inpatients (7-19 years) and their parent caregivers participated in a pilot randomized controlled study to examine the effectiveness of an Immersive VR therapeutic intervention (Stage 2). This mixed methods study reports Stage 1 & 2 quantitative and qualitative data related to VR feasibility and acceptability. Results: Results indicate favorable perceptions from HCPs with respect to ease of use and usefulness of VR, and had positive intentions to use it in the future. Parent caregivers reported highly acceptability of VR for their hospitalized child. Patients reported high satisfaction of the VR intervention within minimal adverse effects. Barriers and facilitators to VR use with seriously ill children and specific recommendations for content development were elicited. Conclusion: This study shows there are several potential clinical uses for Immersive VR intervention, beyond medical procedural distraction, to support psychological adjustment to hospitalization and patient quality of life.