Contemporary manufacturing systems are still evolving. The system elements, layouts, and integration methods are changing continuously, and ‘collaborative robots’ (CoBots) are now being considered as practical industrial solutions. CoBots, unlike traditional CoBots, are safe and flexible enough to work with humans. Although CoBots have the potential to become standard in production systems, there is no strong foundation for systems design and development. The focus of this research is to provide a foundation and four tier framework to facilitate the design, development and integration of CoBots. The framework consists of the system level, work-cell level, machine level, and worker level. Sixty-five percent of traditional robots are installed in the automobile industry and it takes 200 hours to program (and reprogram) them. Integrating CoBots has the potential to enhance the abilities of both the robotic and human actors within the system, improving process efficiencies, and adapting to changes. A thorough review of the literature, safety and layout challenges, and contemporary factory automation configurations using solutions that have been introduced to the market will be presented, as well as a roadmap for education and research challenges.