Transnational city-cooperation is pursued as a means of strengthening a city region’s position in the face of global pressures, where the capacity to ‘jump scales’ is believed to widen the room for manoeuvre. According to the rescaling literature, international activities of city regions, which are currently mushrooming at a global and especially European scale, can be seen as a major vector for city region’s strategies to strengthen their bargaining position in the international marketplace. We therefore analyzed the international activities of five Swiss agglomerations (Zurich, Lucerne, Berne, Lausanne, Geneva), as well as of two European city regions (Stuttgart and Lyon). We show that both the intensity and the content of the international activities are dependent of the economic vulnerability of a city region. Additionally, the EU plays a major role in promoting these networks. The combination of these two factors explains the relative reluctance of the Swiss city regions in this area, whereas the two European cases are clear examples for the increasingly perceived necessity to become engaged in transnational city cooperation in order to stay competitive in the international marketplace.