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Non-climate-related anthropogenic processes and frequently encountered natural hazards exacerbate the risk in coastal zones and megacities and amplify local vulnerability. Coastal risk is amplified by the combination of sea level rise (SLR) resulting from climate change, associated tidal evolution, and the local sinking of land resulting from anthropogenic and natural hazards. In this framework, the authors of this investigation have actively contributed to the joint European Space Agency (ESA) and the Chinese Ministry of Science and Technology (MOST) Dragon IV initiative through a project (ID. 32294) that was explicitly designed to address the issue of monitoring coastal and delta river regions through Earth Observation (EO) technologies. The project’s primary goals were to provide a complete characterization of the changes in target scenes over time and provide estimates of future regional sea level changes to derive submerged coastal areas and wave fields. Suggestions are also provided for implementing coastal protection measures in order to adapt and mitigate the multifactor coastal vulnerability. In order to achieve these tasks, well-established remote sensing technologies based on the joint exploitation of multi-spectral information gathered at different spectral wavelengths, the exploitation of advanced Differential Interferometric Synthetic Aperture Radar (DInSAR) techniques for the retrieval of ground deformations, the realization of geophysical analyses, and the use of satellite altimeters and tide gauge data have effectively been employed. The achieved results, which mainly focus on selected sensitive regions including the city of Shanghai, the Pearl River Delta in China, and the coastal city of Saint Petersburg in Europe, provide essential assets for planning present and future scientific activities devoted to monitoring such fragile environments. These analyses are crucial for assessing the factors that will amplify the vulnerability of low-elevation coastal zones.