The multilateral economic order is facing several major challenges, including the persistent impact of COVID-19 on global output and growth, the shift towards decoupling and fragmentation in economic relations with China, the Russian invasion of Ukraine, the disruption of global value chains, and the rise of conservative populism. Together these challenge the principles of liberal internationalism and provide a clear illustration of the relationship between trade, finance, international institutions, and the difficulties governments face in coping with the problems generated by complex interdependence. This chapter explores past and emerging challenges in the Global Political Economy (GPE) through a range of theoretical lenses. It also pays attention to the significance of race, colonialism, gender, and the intersections of GPE with everyday life.