In this paper, focusing on the European Territorial Cooperation (INTERREG) example, the author compares three selected policy themes to understand what drives cross-border cooperation (CBC) in different contexts. The main argument is that cultural, economic, political, institutional, and geographical drivers of CBC play different roles in determining the intensity of CBC across different themes. To test this argument, three separate regressions are run for the policy themes of education, small and medium sized enterprises, and infrastructure. The regression results support that the intensity of CBC in each particular thematic area is driven by a unique combination of factors. This finding provides important insights on CBC policy-making in the European Union and potentially beyond. Follow-up studies can inform the design of future CBC policies and prioritization of thematic CBC interventions.