Scholars often pay insufficient attention to bridging the research divide between different world regions. The authors argue that structured qualitative comparisons across world regions offer a sound middle ground for the integration of universal approaches and context knowledge. The chapter puts forward suggestions about how to deal with challenges in cross-area comparisons at the conceptual, methodological, and practical level. First, scholars should integrate region-centered academic discourses to foster conceptual advancement and empirical research, thereby overcoming the restricted horizons of specific knowledge communities. Second, systematic research designs and case-selection criteria should be aligned with area awareness to reap the benefits of cross-regional CAS. Third, the authors’ notion of “applied CAS” implies that practical considerations for successful comparative research must be understood as an important constituent of any successful research strategy. Cross-area comparisons are indispensable if social science aims to provide truly universal explanations in touch with the diverse realities of a globalized world.