Moderate to severe pain occurs in many cancer patients during their clinical course and may stem from the primary pathology, metastasis, or as treatment side effects. Uncontrolled pain using conservative medical therapy can often lead to patient distress, loss of productivity, shorter life expectancy, longer hospital stays, and increase in healthcare utilization. Various publications shed light on strategies for conservative medical management for cancer pain and a few international publications have reviewed limited interventional data. Our multi-institutional working group was assembled to review and highlight the body of evidence that exists for opioid utilization for cancer pain, adjunct medication such as ketamine and methadone and interventional therapies. We discuss neurolysis via injections, neuromodulation including targeted drug delivery and spinal cord stimulation, vertebral tumor ablation and augmentation, radiotherapy and surgical techniques. In the United States, there is a significant variance in the interventional treatment of cancer pain based on fellowship training. As a first of its kind, this best practices and interventional guideline will offer evidenced-based recommendations for reducing pain and suffering associated with malignancy.