Human cyber-physical systems comprise of entities in physical and cyber layers that interact with each other, for which a systems design approach is recommended in literature findings. However, multiple systems design approaches exist that may provide guidance on component identification, and interface and interaction definition. In this article, holonic and mereological systems design approaches are compared to consider which is better suited for the development of human cyber-physical systems. Commonalities and differences in the two design approaches are identified and discussed, including multi-level organization and structuring of entities in a human cyber-physical system. Potential implications for systems design are identified, which include enhancement in adaptability and scalability. Applications where holonic and mereological systems design approaches were used to develop systems are highlighted, revealing differences between the focus on control, coordination and composition between the design approaches. In the end, a hybrid approach of the two may benefit the development of human cyber-physical systems, but a holonic systems design approach appears to be better suited to the development of dynamic systems, which human cyber-physical systems are more likely to be. Moreover, a holonic systems design approach is more mature in incorporating human actors into the cyber layer of a human cyber-physical system, in which human capabilities should be fostered through human-system integration as the cornerstone of Industry 5.0.