As manufacturing processes become increasingly digitalized and connected, plenty of attention is given to real-time inventory monitoring, supply chain management, and product quality control, but limited effort is dedicated to monitor operator health and safety risks. Addressing these risks by leveraging Industry 4.0 enabling technologies is critical, as it can lead to significant improvements in terms of social sustainability such as operator well-being as well as manufacturing quality and productivity. The present thesis proposes an operational framework for the identification and management of health and safety risks by utilizing a Human-Cyber-Physical System approach based on continuous monitoring of Operator 4.0-related parameters within an interconnected and sustainable manufacturing environment.