Global economic integration has changed business conditions significantly. Corporations operating internationally and establishing foreign subsidiaries are facing the obligation as well as the challenge to profit from cross-border interaction. However, potential synergetic benefits provided by the international environment are accompanied by even more demanding challenges. This study elaborates to which extend German small and medium-sized manufacturing businesses could benefit from the implementation of a strategic cross-border synergy management. The study is based on a single case study deriving the research hypotheses and a survey investigating cross-border interaction throughout a sample of small and medium-sized manufacturing businesses. Based on the research findings, this paper proposes a holistic framework, designed for strategists of small and medium-sized manufacturing business. It outlines the establishment of the cross-border synergy management concept as part of the corporate strategy and the efficient and effective management of international interaction. 'Synergies are not realized by themselves - they have to be identified and actively developed within a professionally coordinate process. Management of synergy seeking organizations is asked for intensive efforts beyond daily operations' (Weber and Roventa, 2006).