Cancer is one of the major leading causes of death worldwide, with ongoing efforts to identify strategies that can improve quality of life and decrease mortality in this specific population. Through all the incredible advancements in screening tools and medical oncology, patients are now living much longer with cancer, which presents a global challenge on how to best improve their outcomes, with psycho-oncology being an area of significant interest. The mental health of cancer patients is frequently underdiagnosed due to the clinician’s primary focus on the side effects of antineoplastic agents and physical health symptoms. The current literature shows increased mortality and morbidity among cancer patients with concomitant depression and/or anxiety mood disorders; however, presently, there is no standardized optimal combination of therapies that can be offered to these patients. This chapter illustrates the past, existing, and future concepts of psycho-oncology and the different strategies that a provider can utilize and offer patients with cancer, especially in metastatic disease.