This chapter considers interoperability from the perspective of application domains and related business challenges. It first concentrates on automated and collaborative systems ranging from industrial automation, robotics, and manufacturing (including Industry 4.0/5.0 and Smart Manufacturing, cyber-physical systems, and IIoT), to e-Work and e-Activities (e.g., e-Business, e-Commerce, or e-Services), and including collaborative networked organizations. It then discusses the needs and challenges for systems interoperability in the context of collaborative and automated systemsAutomated systems, spanning collaboration between men, machines, and cybernetic systems. Finally, methodological aspects to carry out analysis, design, and implementation of interoperability projects are synthetically explained.