Digital twins (DTs) powered by artificial intelligence (AI) are becoming important transformational tools in healthcare, enabling real-time simulation and personalized decision support at the patient level. The aim of this review is to critically examine the evolution, current applications, and future potential of AI-based DTs in healthcare, with a particular focus on their role in enabling real-time simulation and personalized patient-level decision support. Specifically, the review aims to provide a comprehensive overview of how AI-based DTs are being developed and implemented in various clinical domains, identifying existing scientific and technical gaps and highlighting methodological, regulatory, and ethical issues. Taking a “local to global” perspective, the review aims to explore how individual patient-level models can be scaled and integrated to inform population health strategies, global data networks, and collaborative research ecosystems. This will provide a structured foundation for future research, clinical applications, and policy development in this rapidly evolving field. Locally, DTs allow medical professionals to model individual patient physiology, predict disease progression, and optimize treatment strategies. Hospitals are implementing AI-based DT platforms to simulate workflows, efficiently allocate resources, and improve patient safety. Generative AI further enhances these applications by creating synthetic patient data for training, filling gaps in incomplete records, and enabling privacy-respecting research. On a broader scale, regional health systems can use connected DTs to model population health trends and predict responses to public health interventions. On a national scale, governments and policymakers can use these insights for strategic planning, resource allocation, and increasing resilience to health crises. Internationally and globally, AI-based DTs can integrate diverse datasets across borders to support research collaboration and improve early pandemic detection. Generative AI contributes to global efforts by harmonizing heterogeneous data, creating standardized virtual patient cohorts, and supporting cross-cultural medical education. Combining local precision with global insights highlights DTs’ role as a bridge between personalized and global health. Despite the efforts of medical and technical specialists, ethical, regulatory, and data governance challenges remain crucial to ensuring responsible and equitable implementation worldwide. In conclusion, AI-based DTs represent a transformative paradigm, combining individual patient care with systemic and global health management. These perspectives highlight the potential of AI-based DTs to bridge precision medicine and public health, provided ethical, regulatory, and governance challenges are addressed responsibly.