We live in a complex world in which many skeptics doubt the possibility of global governance and scoff at prospects for global multilateralism. Concomitantly, the deficiencies and dysfunctioal aspects of global governance have prompted some to wish to complement it by constructing diverse layers of multilateralism at the regional and transregional levels. Asian–European interregionalism under the Asia–Europe Meeting (ASEM) has been proposed as an alternative framework to support global governance and a multilateral system. Established in 1996, ASEM has evolved into a multidimensional form of interregionalism, encouraging Asian and European countries to cooperate on a number of fronts, from political and military security to economic and socio-cultural engagement. Since the 2016 summit, ASEM has attempted to assert its relevance beyond trade by emphasizing the connectivity inherent in its scheme of cooperation. While it remains to be seen whether this multilateral initiative will succeed, unresolved challenges linger. The unfinished, open-ended character of ASEM enables us to treat it as an example of contemporary efforts to secure multilateralism. Can Asian and European regional entities, originally the expressions of the power and interests of regional states, strike a balance among their national, regional, and global interests and amicably deploy their power to safeguard multilateralism and support global governance?