People with severe mental disorders (SMDs) have a higher mortality rate and reduced life expectancy compared to the general population. Factors that contribute to higher mortality rates include a higher rate of smoking and increased incidence of obesity from lifestyle, diet, or medication side effects. Cancer treatment may exacerbate mood and psychotic symptoms in patients with SMD. Some of the medications used in cancer treatment or the medications used to alleviate the side effects of cancer treatment can have adverse reactions with psychotropic medications. This article examines problems that patients with SMD encounter with their cancer diagnosis and treatment. Oncology nurses in any clinical setting play a pivotal role in identifying the special needs of a patient with SMD and must become familiar with psychosocial issues, psychotropic medications, and SMD to educate and advocate for these patients and their families. Collaborating and coordinating care between oncology and psychiatry providers is needed for optimal patient outcomes.