Understanding the impacts on the Brazilian semi-arid coast, which is a drought-prone area (>1000 km) in the tropical Atlantic, and how ecosystems survive and adapt to such extreme environments requires socioecological studies to create a theory for conservation. Here, we highlight five main ongoing changes in tropical semi-arid areas, namely (1) the decrease in rainfall rates due to climate change, which alters freshwater flows, alters water residence times, and promotes hypersalinity (>37) in low-inflow estuaries; (2) sea-level rise, groundwater hazards, increased erosion of beaches and nearshore mangroves, and landward mangrove forest expansion due to enhanced saline intrusion along river basins; (3) the decrease in land-ocean fluxes due to silting and closure of sandy bars in estuarine mouths; (4) warming and increased intensity and frequency of extreme events (e.g., heat waves, droughts, and sea swells); and (5) growing eutrophication and hypoxia, loss of vegetation cover and biodiversity due to urbanization, aquaculture (shrimp farming), agriculture, and land-use change, which includes building dams for water supply. The alteration of biogeochemical processes (“Arctic Paradox” hypothesis) and acidification that potentialize the impact of contaminants and nutrients is also highlighted. These impacts have effects on food and water security and multiple trophic levels, which should preferentially be studied through a long-term approach for advancing research. Based on these concerns, we propose key questions that should guide research in the context of the Decade of Ocean Science for Sustainable Development (2021–2030) to support science-based management actions in Brazil and other similar semi-arid areas worldwide.