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Unhoused individuals are at high risk for chronic illness and early mortality. For those who have serious or life-limiting illness, being unhoused can negatively impact symptom management, access to disease-modifying therapies, and ability to receive goal-concordant care at the end of life (EOL). Palliative care (PC) clinicians should be prepared to take a thorough housing history, identify barriers to care, and work with patients and teams to devise care plans that are realistic and in line with the patient's preference and values. In this article, an interdisciplinary group of PC, internal medicine, psychiatry, and addiction medicine clinicians and researchers with expertise in caring for unhoused patients present an overview of the assessment and management of patients with serious illness who are unhoused. We outline key considerations for addressing symptoms associated with serious illness, engaging in Advance Care Planning, evaluating for comorbidities and mental health concerns, and coordinating medical therapies for the patient's underlying serious illness.