This paper is based on the second stage of a Design-Based Research (DBR) project encompassing the initial prototyping of virtual reality (VR) simulation in Paramedicine education using self-reported and biometric feedback data. In this discussion paper we present the range of reflections and theoretical possibilities that arose from the piloting experience, and their implications in re-designing practice in Paramedicine education. We focus on the foundational literature and epistemological understandings coming from neurophenomenological cognitive science applied in technology-enhanced learning, using mixed reality (MR) in Paramedicine simulation learning as a case. We do so following the logic of a DBR methodological framework, in part demonstrating the usefulness of DBR when reflecting on applied practice to inform newer theoretical developments leading to further integrated solutions in future practice. In addition, we also put attention on a conceptual shift from a focus on VR, to a focus on MR with emphasis on the associated benefits offered by MR learning situations within Paramedicine education. Finally, we discuss the benefits of incorporating self-reported and biometric feedback data in Paramedicine education in particular, and in technology-enhanced learning in general, for the design of meaningful learning experiences informed by emotional and physiological responses of learners.