Older adults with cancer reporting fatigue and sleep disorders often have coexisting geriatric syndromes and are at high risk of further functional decline. This review summarizes special considerations in the diagnosis and treatment of sleep disorders and fatigue when older persons with cancer present with multiple comorbidities, polypharmacy, dementia, delirium, and/or falls. Physicians caring for these older adults need to be aware of the unique diagnostic and treatment concerns in this population so that these patients can receive optimal care.