Territorial management in the Amazon region of Brazil presents essential challenges for the coming years, considering the unresolved problems of the central government instrument, the Economic Ecological Zoning of the EEZ, and the changes that are taking place in this territory. The EEZ is an instrument that has been applied at different scales for more than 30 years. Still, it has yet to overcome the problems related to the diverse and profound pressures on the environment and the poor quality of the social and economic development of the population. Climate modifications, deforestation, environmental degradation, expansion of mining activities, water flow alterations, and human occupation and urbanization processes are some of the changing factors contributing to significant uncertainties in the region. In this sense, the article presents, based on its own experiences, government information, and data and interviews with managers who worked in the elaboration of the EEZ, a reflection on the main obstacles resulting from the implementation of the EEZ and the changes in the development processes in the region (increasing demand for energy, economic production based on natural resources, climate change). Finally, possible ways of overcoming these challenges are presented, considering methodological guidelines, governance, and forms of social participation.