To profit from cost differences, growth opportunities in emerging markets, lower transaction costs, and fewer trade barriers, manufacturing companies have strongly driven their internationalization efforts over recent decades. Today, these companies produce at globally distributed manufacturing sites and the individual steps of the value chain take place at different locations in the network. However, uncertainties caused by shifting economic forces, conservative winds, and protectionism as well as events such as the COVID-19 pandemic reveal the strong vulnerability of International Manufacturing Networks. Consequently, companies are reevaluating their optimization efforts of often opposing target dimensions such as efficiency, flexibility, time, and quality. In this chapter, we examine today’s business environment of International Manufacturing Networks and its implications on the management of those networks by presenting relevant success factors.