The twin transition, involving digital and circular factors, urgently asks for a systemic change that involves the reconfiguration in the design of products, systems, business models, consumption patterns, and supply chains. Digital technologies play a strategic role in this path, requiring to be adequately deployed and employed in companies’ organizations and processes. In this scenario, different working profiles and roles characterized by new skills are needed. Indeed, industrial and logistic systems need a new sustainable and digital-driven approach to be capable of ensuring a higher equipment effectiveness through a safe, reliable, and efficient management of data and information. In addition, this would enable operators and managers to process cognitive actions and improve the degree of human-machine interaction, becoming effectively integrated with production systems through the adoption and exploitation of digital technologies. Finally, new assessment methods are needed to measure the progresses towards circularity and ensure the reaching of the Net-Zero goals, while supply chain cooperation becomes crucial for the effective realization of servitized and circular strategies, as companies become more joined through closed loops and industrial symbiosis dynamics.