While many companies worldwide are still striving to adjust to Industry 4.0 principles, the transition to Industry 5.0 is already underway. Under such a paradigm, Cyber-Physical Human-centered Systems (CPHSs) have emerged to leverage operator capabilities in order to meet the goals of complex manufacturing systems towards human-centricity, resilience and sustainability. This article first describes the essential concepts for the development of Industry 5.0 CPHSs and then analyzes the latest CPHSs, identifying their main design requirements and key implementation components. Moreover, the major challenges for the development of such CPHSs are outlined. Next, to illustrate the previously described concepts, a real-world Industry 5.0 CPHS is presented. Such a CPHS enables increased operator safety and operation tracking in manufacturing processes that rely on collaborative robots and heavy machinery. Specifically, the proposed use case consists of a workshop where a smarter use of resources is required, and human proximity detection determines when machinery should be working or not in order to avoid incidents or accidents involving such machinery. The proposed CPHS makes use of a hybrid edge computing architecture with smart mist computing nodes that processes thermal images and reacts to prevent industrial safety issues. The performed experiments show that, in the selected real-world scenario, the developed CPHS algorithms are able to detect human presence with low-power devices (with a Raspberry Pi 3B) in a fast and accurate way (in less than 10 ms with a 97.04% accuracy), thus being an effective solution (e.g., a good trade-off between cost, accuracy, resilience and computational efficiency) that can be integrated into many Industry 5.0 applications. Finally, this article provides specific guidelines that will help future developers and managers to overcome the challenges that will arise when deploying the next generation of CPHSs for smart and sustainable manufacturing.