In this monograph, the authors demonstrate how the integration of adaptability, operability, and re-configurability in the design of complex systems is indispensable for the further digitization of engineering systems in smart manufacturing. Globalization of the customer base has resulted in distributed and networked manufacturing systems. However, current design methods are not suitable to address variations in product design, changes in production scale, or variations in product quality necessitated by dynamic changes in the market. Adaptability, operability, and re-configurability are key characteristics that are necessary to address the limitations of the current methods used to design networked manufacturing systems. In recent years, the digital transformation driving Industry 4.0 has had an enormous impact on globally distributed manufacturing. Digitalisation, the integration of digital technology into networked engineered systems, is increasingly being adopted to respond to changes in the market. This is achieved by means of (a) the concurrent design of adaptable systems, (b) addressing flexibility in design parameters, (c) conducting an operability analysis, and (d) employing a reconfiguration strategy to address faults and variances in product quality and re-establish connectivity among the elements in the system. The design of manufacturing systems in the age of Industry 4.0 is addressed in this monograph. The authors introduce the concept of a ‘smart platform’ and a computational framework for the digitalization of networked manufacturing systems. They also suggest how the framework and techniques in this monograph are applicable beyond the manufacturing domain for architecting networked engineered systems in other industries such as chemical processes and health care, that are being transformed through the adoption of the Industry 4.0 construct.