Synergy of Artificial Intelligence and Extended Reality in Patient-focused Health and Well-Being Applications—A Systematic Review

Individually, AI and Extended Reality (XR) have improved patient-oriented care across healthcare domains. Additionally, recent reviews have highlighted the significant synergistic effects of AI and XR in various fields, including healthcare. This review aims to identify existing AI-XR applications for patient-oriented health and well-being, analyze their benefits, derive trends, identify challenges, and outline future perspectives. Articles of any study design published before 9 July 2024 were systematically collected from six databases. After the initial screening of 4,612 articles, 64 matched the eligibility criteria. The applications demonstrated patient benefits, including improved clinical outcomes, engagement, and accessibility. Machine learning, deep learning, and conversational avatars were combined with XR’s interactive environments to enable personalized rehabilitation and physical therapy, mental health, and developmental care interventions. Associated challenges included the technological immaturity of current applications, lack of large-scale validations, and ethical concerns. While innovation in rehabilitation applications reached its peak, future directions include the need for comprehensive validation and investments in technical, regulatory, and clinical integration. Another perspective highlights the potential of combining XR environments with recent trends in generative AI, especially for mental health interventions. Generalized AI-XR paradigms can guide user-centered development through improved human–computer interaction in various computational research fields.