Digital immersive technologies have become increasingly prominent in clinical research and practice, including medical communication and technical education, serious games for health, psychotherapy, and interfaces for neurorehabilitation. The worldwide enthusiasm for digital health and digital therapeutics has prompted the development and testing of numerous applications and interaction methods. Nevertheless, the lack of consistency in the approaches and the peculiarity of the constructed environments contribute to an increasing disparity between the eagerness for new immersive designs and the long-term clinical adoption of these technologies. Several challenges emerge in aligning the different priorities of virtual environment designers and clinicians. This article seeks to examine the utilization and mechanics of medical immersive interfaces based on extended reality and highlight specific design challenges. The transfer of skills from virtual to clinical environments is often confounded by perceptual and attractiveness factors. We argue that a multidisciplinary approach to development and testing, along with a comprehensive acknowledgement of the shared mechanisms that underlie immersive training, are essential for the sustainable integration of extended reality into clinical settings. The present review discusses the application of a multilevel sensory framework to extended reality design, with the aim of developing brain-centered immersive interfaces tailored for therapeutic and educational purposes. Such a framework must include broader design questions, such as the integration of digital technologies into psychosocial care models, clinical validation, and related ethical concerns. We propose that efforts to bridge the virtual gap should include mixed methodologies and neurodesign approaches, integrating user behavioral and physiological feedback into iterative design phases.