In an era of rapid technological advancement, the need for effective human-computer interfaces is more crucial than ever. Training professionals, such as engineers, astronauts, and pilots, is increasingly challenging due to the obsolescence of traditional tools, particularly in deep space missions where long distances hinder communication with mission control. Additionally, current training environments often overlook the psychological well-being of the human, which is crucial for sustaining mission endurance. This study presents an innovative framework for supporting the Psychological Well-Being of Astronauts in Deep Space Missions through Virtual and Mixed Reality Technologies. Our approach focuses on virtual environments that stimulate key neurochemicals, such as oxytocin, which contribute to emotional regulation, stress resilience, and mental well-being. By leveraging insights from neuroscience, human-computer interaction, immersive technology, and Artificial Intelligence, we introduce a novel research methodology designed to also measure the well-being in deep space missions. We provide a concise overview of the framework’s steps and use cases, demonstrating its feasibility and potential impact. This paper aims to establish our framework as a vital foundation for future empirical research, thereby enhancing the preparation and well-being of astronauts for critical deep space missions. We also demonstrate that the conceptual framework is feasible and serves as a foundation for future empirical studies, where the proposed Framework can be implemented, refined, and validated through experimental research.