Industry 5.0 (I5.0) is a novel paradigm for the development and deployment of industrial applications based on Cyber-Physical Systems (CPS). It evolves Industry 4.0 in directions that exploit trustworthy human–AI interactions in human-in-the-loop scenarios. Despite the rising popularity of I5.0, there is still a lack of reference architectures (RAs) that outline the building blocks of I5.0 applications, along with the structuring principles for effectively integrating them in industrial systems. This chapter introduces a reference model for industrial applications that addresses critical elements and requirements of the I5.0, including human–robot collaboration, cybersecurity, safety, and trust. The model enhances state-of-the-art I4.0 Industrial Internet of Things (IIoT) architectures with human-centered I5.0 features and functionalities. Based on this model, the present chapter introduces a set of blueprints that could ease the development, deployment, and operation of I5.0 applications. These blueprints address technical integration, trustworthy operations, as well as the ever-important compliance to applicable regulations such as General Data Protection Regulation (GDPR) and the emerging AI Act.