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This paper analyses interregional relations between the European Union (EU) and Latin America and the Caribbean (LAC) in the context of recent transformations in the international system. It addresses the following question: how can a strategic partnership between the EU and LAC be rethought in a global environment marked by growing uncertainty? To answer this, the study examines the effects of shifting dynamics of globalisation, the reconfiguration of the international order, and intensifying geopolitical tensions—particularly the strategic rivalry between the United States and China. First, it presents an analysis of the current geopolitical and geoeconomic landscape and its implications for the interregional agenda, identifying both structural constraints and emerging opportunities. Second, it explores the recent revitalisation of trade negotiations between the two regions, with particular attention to the EU–Chile, EU–Mercosur, and EU–Mexico agreements. Finally, drawing on a critical international political economy perspective, the paper offers reflections on the challenges of achieving strategic autonomy for both regions.