As a geostrategic space promoted by the US and its allies, the Indo-Pacific regional architecture is being shaped up with multi-directional, multi-layered, and increasingly fragmented trends. While the US is strengthening its hub-and-spoke alliance structure into a network system through lattice-work mechanisms, China advocates multilateralism while seeking to draw the Global South into new initiatives linked to its Belt and Road grand strategy. In an increasingly polarized world, ASEAN’s centrality faces numerous challenges. Nevertheless, efforts to strengthen linkages among middle powers and the restructuring of the global system also offer certain economic and political opportunities for ASEAN’s members to participate in shaping a new regional order.