This overview article describes the design and use space of integrating humans and cyber-physical systems in Industry 4.0, with special regards to the interplay of analysis, design and evaluation methods and phases. Starting with an introduction into the challenges of Industry 4.0 and an overview on existing methods of system design, the design and use space of method models is described and exemplified with examples from Industry 4.0. An extended U-Method of iterative analysis, design and evaluation is derived, described in theory and exemplified with practical examples. An outlook identifies potential roadmaps of future design and evaluation methods especially for industry 4.0.