This chapter sets out the study’s comparative design and methodological approach. The book combines a large-N investigation of transnationalism-related public opinion across contemporary European metropolises—based on European Social Survey data—with an in-depth analysis of voting and its determinants across the boroughs of two European capital cities: London and Rome. These two metropolises are selected as “least similar cases” that differ on many dimensions yet share a strong restructuring of their countries’ politics by the transnational cleavage. The chapter introduces the selection of sub-metropolitan spatial units for the analyses, the logic of comparison, and the ten hypotheses guiding the empirical research. Three empirical parts are outlined: the analysis of metropolitan public opinion, electoral behaviour, and compositional and contextual effects on voting for GAL-TAN parties within London and Rome. The chapter thus explains the robust research design adopted to test whether, and how, metropolitan political geography reflects Europe’s new cultural cleavage.