This theoretical essay develops a neuroeducational framework for inclusive instructional design in complex educational contexts, integrating the principles of Daniel Siegel’s interpersonal neurobiology with special education methodologies. A critical review of the literature highlights how managing the ‘window of tolerance’ and affective co-regulation mechanisms are fundamental elements for the effectiveness of educational interventions in vulnerable situations, particularly in hospital school settings. The proposed framework goes beyond the ‘dual-track design’ approach through an integrated model that emphasizes the interconnection between neurobiological processes, emotional dimensions, and learning. Theoretical implications indicate the need to redefine the professional competencies of specialized teachers by incorporating neuroeducational knowledge, interpersonal attunement strategies, and adaptive methodologies. Practical applications include systemic observation protocols, process-based assessment tools, and guidelines for designing neurobiologically informed learning environments in hospital and home-based services.