Hospitalized patients with palliative care needs often have high levels of physical and psychological symptom distress. Virtual reality (VR) with a music therapy intervention may improve physical and psychological symptoms. To assess symptom distress and quality of life (QOL) among hospitalized palliative care patients who participated in a virtual reality-based music therapy (VR-MT) intervention, and to explore VR-MT from the perspectives of health care professionals involved in their care. Single-arm pilot study of a two-day VR-MT intervention. Patients seen by an inpatient palliative care consultation service at a U.S. hospital could participate in the VR-MT intervention. Participants created a customized soundtrack with a music therapist and then listened to it while experiencing a 360-degree VR nature-based environment of their choice. Patients completed the Edmonton Symptom Assessment System, revised version (ESAS-r) and McGill Quality of Life, revised version (MQOL-R) before and after VR-MT. Members of the participants' health care teams were interviewed. Seventeen patients completed VR-MT (range 20-79 years of age, 59% women). Moderate clinical improvements were observed for total ESAS-r score (Cohen's d effect size, 0.68), physical distress subscale (0.52), and psychological distress subscale (0.60); small improvements were observed in total MQOL-r score (0.26) and the existential subscale (0.27). Health care team members described the value of VR-MT as facilitating meaningful conversations. This pilot study of VR combined with a music therapy intervention for hospitalized patients with palliative care needs supports opportunities for future study of potential improvements in symptom distress and QOL.