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Abstract Industry 4.0 is based on the digitization of manufacturing industries and has raised the prospect for substantial improvements in productivity, quality, and customer satisfaction. This digital transformation not only affects the way products are manufactured but also creates new opportunities for the design of products, processes, services, and systems. Unlike traditional design practices based on system-centric concepts, design for these new opportunities requires a holistic view of the human (stakeholder), artefact (product), and process (realization) dimensions of the design problem. In this paper we envision a “human-cyber-physical view of the systems realization ecosystem,” termed “Design Engineering 4.0 (DE4.0),” to reconceptualize how cyber and physical technologies can be seamlessly integrated to identify and fulfil customer needs and garner the benefits of Industry 4.0. In this paper, we review the evolution of Engineering Design in response to advances in several strategic areas including smart and connected products, end-to-end digital integration, customization and personalization, data-driven design, digital twins and intelligent design automation, extended supply chains and agile collaboration networks, open innovation, co-creation and crowdsourcing, product servitization and anything-as-a-service, and platformization for the sharing economy. We postulate that DE 4.0 will account for drivers such as Internet of Things, Internet of People, Internet of Services, and Internet of Commerce to deliver on the promise of Industry 4.0 effectively and efficiently. Further, we identify key issues to be addressed in DE 4.0 and engage the design research community on the challenges that the future holds.