In the context of European integration, cross-border cooperation has become increasingly important. Following both the quantitative and qualitative expansion of this policy-field, it has repeatedly been the subject of scientific analysis in the past. However, as a result of the classical differentiation of the scientific system, it was mostly viewed from a monodisciplinary perspective. This publication aims at the foundation of a trans-disciplinary research approach in the field of European cross-border cooperation. It takes the multi-dimensional reality of practical territorial cooperation in Europe as a starting point and develops a transdisciplinary scientific approach. Based on a common analytic frame of reference, practical patterns of cross-border policy-making in different European border regions are analyzed from the integrated theoretical perspectives of various scientific disciplines: Political Science, Geography, Sociology, History, Law, Cultural Sciences and Socio-Linguistics, Economics and Administrative Science. The scientific conceptualizations are expanded by reports from practitioners coming from different institutional and functional levels of European cross-border policy-making.