Cyber-physical-human systems (CPHS) are smart products and systems that offer services to their customers, supported by back-end systems (e.g., information, finance) and other infrastructure. In this paper, initial concepts and research issues are presented regarding the generative design of CPHS and CPHS families. Significant research gaps are identified that should drive future research directions. The approach proposed here is a novel combination of generative and configuration design methods with product family design methodology and an explicit consideration of usability across all human stakeholders. The need for a new CPHS transdiscipline is identified. With the proposed approach, a wide variety of CPHS, including customized CPHS, can be developed quickly by sharing technologies and modules across CPHS family members, while ensuring user acceptance. The domain of assistive technology is used in this paper to provide an example field of practice that could benefit from a systematic design methodology and opportunities to leverage technology solutions.