The policy of the European Union, which promotes a vision of Europe without borders and has fostered the development of cooperation across borders over 25 years, has led, in some parts of Europe, to the emergence of so-called integrated cross-border regions. Thus far, the increase of cross-border flows and interactions has always been a normative and almost unquestioned policy paradigm. However, tendencies of re-bordering and signs of growing Euroscepticism can also be observed nowadays in these border regions, which show the importance of investigating the negative externalities that can be generated by cross-border integration. This article attempts to do this by focusing on three case studies usually considered as among the most integrated ones in Europe because of cross-border flows related to work: the cross-border metropolitan regions of Basel, Geneva and Luxembourg. Our findings show that if several decades of cross-border integration have led to the reinforcement of the functional linkages between the border regions, some effects of the cross-border integration process have also created a functional specialisation of space that relies on social and economic inequalities. Such a situation contradicts the ideal of cross-border territorial cohesion and helps to better understand the rise of Euroscepticism in some of the border areas.