Drylands cover about 40% of the world’s land area and support two billion people, most of them living in developing countries that are at risk due to land degradation. Over the last few decades, there has been warming, with an escalation of drought and rapid population growth. This will further intensify the risk of desertification, which will seriously affect the local ecological environment, food security and people’s lives. The goal of this research is to analyze the hydrological and land cover characteristics and variability over global arid and semi-arid regions over the last decade (2010–2019) using an integrative approach of remotely sensed and physical process-based numerical modeling (e.g., Global Land Data Assimilation System (GLDAS) and Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (FLDAS) models) data. Interaction between hydrological and ecological indicators including precipitation, evapotranspiration, surface soil moisture and vegetation indices are presented in the global four types of arid and semi-arid areas. The trends followed by precipitation, evapotranspiration and surface soil moisture over the decade are also mapped using harmonic analysis. This study also shows that some hotspots in these global drylands, which exhibit different processes of land cover change, demonstrate strong coherency with noted groundwater variations. Various types of statistical measures are computed using the satellite and model derived values over global arid and semi-arid regions. Comparisons between satellite- (NASA-USDA Surface Soil Moisture and MODIS Evapotranspiration data) and model (FLDAS and GLDAS)-derived values over arid regions (BSh, BSk, BWh and BWk) have shown the over and underestimation with low accuracy. Moreover, general consistency is apparent in most of the regions between GLDAS and FLDAS model, while a strong discrepancy is also observed in some regions, especially appearing in the Nile Basin downstream hyper-arid region. Data-driven modelling approaches are thus used to enhance the models’ performance in this region, which shows improved results in multiple statistical measures ((RMSE), bias (ψ), the mean absolute percentage difference (|ψ|)) and the linear regression coefficients (i.e., slope, intercept, and coefficient of determination (R2)).