Managing patients with musculoskeletal metastatic disease involves complex ethical challenges, particularly in shared decision-making (SDM), prognostic uncertainty, and end-of-life considerations. This chapter examines key ethical principles that guide care, focusing on relational autonomy and SDM frameworks, strategies for reconciling realistic treatment goals with patient expectations, and tools to support prognostic clarity. Although medical decision-making has shifted from a paternalistic approach to a more patient-centered one, challenges remain in ensuring truly informed consent and minimizing undue influence from caregivers or clinicians. Discrepancies between patient and physician priorities often occur, particularly when patients prioritize symptom relief over potential adverse effects, and highlight the need for personalized care. Prognostic tools such as the PATHFx calculator and the Scandinavian Sarcoma Group scoring system can assist clinicians in establishing realistic expectations and encouraging end-of-life discussions. Additionally, racial disparities in prognostic communication and patient optimism about treatment options highlight the importance of early palliative care and culturally sensitive dialogue. The ethical management of musculoskeletal metastatic disease requires multidisciplinary collaboration, transparent communication, and a better understanding of prognosis. Systematically implementing SDM frameworks and evidence-based tools helps clinicians better support patients’ treatment decisions that align with their individual values while maintaining realistic outcome expectations.