question: Patients with cancer are living longer, and many experience pain secondary to tumor invasion or as a consequence of cancer-directed therapies. Opioid use disorders and associated morbidity and mortality have increased with dramatic rise during the SARS-CoV-2 pandemic. National and international stakeholders have developed clinical practice guidelines in an effort to curb opioid misuse and overdose-related death. However, to ensure that patients with cancer do not experience barriers to adequate pain management, most of these guidelines are not intended for patients with cancer-related pain or for those receiving palliative or hospice care. Oncology, palliative, and hospice care providers are increasingly tasked with the management of severe disease-related pain in the setting of coexisting opioid use disorder without research on the most effective risk and harm reduction strategies to guide care. Clinicians should be familiar with addiction medicine and chronic pain literature and be able to incorporate some of these best practices. This case study reviews the management of severe cancer-related pain in a patient with co-occurring opioid use disorder, utilizing many of the best practices in available clinical practice guidelines for the management of chronic non-cancer-related pain.