Objective: Expatriate nurses constitute a large proportion of the healthcare workforce in many Middle Eastern countries, including Saudi Arabia. Providing end-of-life (EOL) care in culturally diverse environments can present significant challenges, particularly when linguistic, cultural, and religious differences influence communication and decision-making processes. Understanding these challenges is essential to improving culturally responsive EOL care. Methods: A mixed-methods systematic review was conducted to synthesise evidence on expatriate nurses’ experiences of providing end-of-life care in Middle Eastern healthcare settings. Electronic databases were searched for relevant studies, and eligible studies were selected based on predefined inclusion criteria. Methodological quality of the included studies was assessed using appropriate appraisal tools. Data were extracted and synthesised using a narrative thematic approach to integrate qualitative and quantitative findings. Results: Nine studies met the inclusion criteria and were included in the review. The synthesis identified five major themes influencing expatriate nurses’ experiences of providing EOL care: communication barriers, cultural and religious challenges, organisational and structural constraints, the role of families in decision-making, and compassionate care and professional coping strategies. Language discordance, particularly limited Arabic proficiency, emerged as a major barrier affecting communication with patients and families. Cultural expectations surrounding family involvement and religious practices also influenced nurses’ ability to navigate EOL discussions. Organisational factors such as heavy workloads and limited palliative care training further constrained the delivery of holistic care. This review highlights the complex linguistic, cultural, and organisational factors affecting expatriate nurses’ ability to deliver effective end-of-life care in Middle Eastern healthcare settings. Strengthening language support systems, enhancing cultural competence training, and improving institutional support mechanisms may help improve the quality of EOL care for culturally diverse patient populations.