The importance of the Amazon region for contemporary geopolitics has become increasingly prominent. This chapter explores how the strategic geopolitical position of the Amazon region, in view of the growing global demand for natural resources in the twenty-first century, is shaping Brazil’s economic and sustainable development policies and sovereignty over the region. Our hypothesis is that the Amazon region is becoming the epicentre of global geopolitical attention due to its wealth of strategic resources, including water, minerals, and biodiversity. This demands a greater presence of the Brazilian state to boost economic growth, sustainable development, the defence of regional sovereignty, and its protection. Based on this design, we propose a general objective and three specific ones that will guide the methodology of the work, encompassing a bibliographical review—based on classic concepts in the area such as sovereignty, as well as the most recent debates—and the analysis to be conducted. The general objective is to analyse the new geopolitical configuration of the Amazon region in the context of the growing global demand for natural resources, examining how this affects Brazilian policies and strategies in the region. The specific objectives are: (i) to investigate the relevance of natural resources in the region, such as water, minerals and biodiversity and the growing global demand for natural resources; (ii) to evaluate Brazil’s policies and strategies for promoting economic growth and sustainable development in the Amazon region, considering the responsible exploitation of natural resources; and (iii) to examine the challenges and issues related to Brazilian sovereignty over the Amazon region in a context of intense international attention and demand for its natural resources. The aim of this chapter is to present an overview of the issue, as well as Brazil’s role in this region.