AbstractIn the context of Industry 5.0, characterized by the human-centred transformation of manufacturing processes, assessing operator risk is crucial for ensuring workplace safety and well-being. In this respect, this paper presents the development of a human-cyber-physical system (HCPS) capable of estimating operator risk by leveraging diverse sensing data. By comprehensively analysing complex patterns and interactions among physiological, environmental, and manufacturing variables, the HCPS offers an advanced approach to operator risk assessment. Through the integration of cutting-edge sensing technologies, real-time data collection, and sophisticated analytics paradigms, the HCPS accurately identifies meaningful patterns and anomalies. It dynamically adapts to changing manufacturing conditions, generating risk profiles for operators and work processes. Timely alerts and notifications enable proactive interventions, enhancing safety measures and optimizing work processes. The HCPS empowers decision-making and supporting the well-being and productivity of operators in the Industry 5.0 paradigm, while maintaining a safe working environment. A simulated case study is reported to validate the proposed framework on a variety of industrial scenarios.