Simulation has evolved from basic practice to Immersive Extended Reality (I-XR). This systematic review examined 56 published studies on the impact of I-XR, including virtual reality (VR), augmented reality (AR), and mixed reality (MR), on the education of medical and nursing students, specifically their skill competency, and knowledge acquisition. The results demonstrate the significant potential of I-XR in healthcare education, with 42.5% of VR studies, 42.9% of AR studies, and the single MR study also demonstrating greater improvements in clinical skills and knowledge acquisition compared to non-immersive (non-I-XR) training conditions. In contrast, only 2.5% of VR studies and 7.14% of AR studies favored non-I-XR methods. It is important, however, to acknowledge the 26.8% of studies that showed mixed results (some evidence for the I-XR methods on some outcomes, but also some evidence for the non-I-XR methods, on other outcomes). Notably, the review also identified a critical gap in the theoretical foundations of I-XR learning, highlighting the urgent need for research to inform the effective pedagogical implementation of these powerful tools. We offer a preliminary framework to address the lack of learning theory in healthcare I-XR training, with implications for pedagogical practices.