The chapter places foreign policy in-between the systemic dimension of international relations and national politics, thus addressing how governments and national leaders in Southern regional powers respond both to geopolitics/geoeconomics and domestic interests when they formulate foreign policy priorities. In this sense, foreign policy is scrutinized both as a constituent of a state policy confronted with structural needs for survival and security, and as a public policy challenged by the political coalitions and development priorities stemming from electoral results in democratic regimes. Building on Brazil’s recent experience, the chapter approaches the issue of tensions between economic and political interests in the making of foreign policy and analyzes Brazil’s role in multilateral negotiations and its main graduation dilemmas.