In recent years we have experienced several counter-pressures to reverse globalization and reduce the interdependence that has characterized the economic environment for decades. Geopolitical tensions, climate change, and digitalization are some of the megatrends driving this shift from global to more localized and regional business activities. Given the vulnerability of manufacturing global value chains (GVCs) to external shocks, this chapter explores the fundamental aspects of value chain management and the restructuring necessary to adopt a more regional footprint while addressing the new challenges of globalization.