The international system is characterized by increasingly interdependent and asymmetrical relations between the constellations of actors that compose it. While the state remains a central reference in international relations, multilevel and multidimensional relationships make the system very complex. The state, international organizations, non-state actors, club diplomacy and groups of states (e.g., the Group of 20 [G20] and the BRICS grouping of Brazil, Russia, India, China and South Africa) all contribute to this complexity and make the global governance system increasingly multifaceted. In this context, this article examines the relationship between the European Union and the BRICS — two very different actors, pursuing formal and informal integration processes, respectively — and assesses the possibilities and limits of cooperation. This article seeks to understand whether the EU–BRICS relationship reflects a strategic partnership or a structural disjuncture. It starts by discussing multilateralism as a cooperation-oriented but sometimes interest-driven tool in a diverse and multilevel governance system. It then analyses EU–BRICS relations, identifying the main drivers and highlighting how complex context both facilitates and hinders the constitution of this relationship. The article concludes that the EU–BRICS relationship is informed by asymmetries and ambivalence that reflect their different sizes, capacities and approaches. Moreover, although there is a shared understanding that cooperation might be beneficial, contradictory rules and perspectives on international order mean this potentially positive relationship is nevertheless embedded in fundamental structural constraints.