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The global rise of chronic diseases requiring long-term management highlights the need for effective palliative care. Nurses play a central role in providing this care, yet frequently face ethical challenges such as moral distress, complex decision-making, and occupational stress. This systematic review aimed to identify, categorize, and synthesize evidence on nurses’ ethical perspectives, challenges, and professional interventions in palliative care for patients with chronic diseases in both hospital and home settings. The review addressed the following questions: (1) What are nurses’ ethical perspectives in delivering palliative care ? (2) What ethical challenges and decision-making dilemmas do they encounter? (3) Which strategies and interventions support ethically sound care? Following PRISMA 2020 guidelines, five databases (PubMed, Scopus, Web of Science, SID, and Magiran) and gray literature via Google Scholar were systematically searched for studies published between 2015 and 2025 in English or Persian. Eligible studies included qualitative, quantitative, mixed-methods, and peer-reviewed reviews addressing nurses’ ethical challenges in palliative care. Qualitative data were analyzed using inductive content analysis, quantitative findings were synthesized descriptively, and mixed-methods results were integrated to allow convergence across study designs. Extracted codes were organized into themes, grouped into categories, and synthesized into overarching domains. Thirty-four studies met inclusion criteria. Four main domains of ethical challenges emerged: (1) Clinical decision-making and patient autonomy—dilemmas regarding life-sustaining treatments, medication and fluid management, palliative sedation, and conflicts between patient preferences and family/cultural expectations; (2) Justice and resource allocation—insufficient ethics education, high workload, limited organizational support, poor interprofessional collaboration, and scarce resources; (3) Beneficence and patient-centered care—ethical issues related to technological innovations, informed consent, data privacy, and environmental pressures such as ICU or emergency care conditions; (4) Non-maleficence and moral distress prevention—moral distress, burnout, reduced ethical courage, and legal concerns affecting clinical decisions. Nurses encounter substantial ethical challenges in delivering palliative care for patients with chronic diseases. Addressing these challenges requires ethics education, structured organizational guidance, interprofessional collaboration, and context-sensitive strategies to safeguard patient dignity and reduce moral distress. These findings provide evidence for policymakers, educators, and managers to develop practical interventions and ethical frameworks across diverse care settings.