Land-use changes adversely may impact ecological entities and humans by affecting the water cycle, environmental changes, and energy balance at global and regional scales. Like many megaregions in fast emerging countries, Tamil Nadu, one of the largest states and most urbanized (49%) and industrial hubs in India, has experienced extensive landuse and landcover change (LULC). However, the extent and level of landscape changes associated with vegetation health, surface permeability, and Land Surface Temperature (LST) has not yet been quantified. In this study, we employed Random Forest (RF) classification on Landsat imageries from 2000 and 2020. We also computed vegetation health, soil moisture, and LST metrics for two decades from Landsat imageries to delineate the impact of landscape changes in Tamil Nadu using Google Earth Engine (GEE). The level of vegetation health and drought for 2020 was more accurately assessed by combining the Temperature Condition Index (TCI) and Vegetation Condition Index (VCI). A Soil moisture index was subsequently used to identify surface permeability. A 75% expansion in urban areas of Tamil Nadu was detected mainly towards the suburban periphery of major cities between 2000 and 2020. We observed an overall increase in the coverage of urban areas (built-up), while a decrease for vegetated (cropland and forest) areas was observed in Tamil Nadu between 2000 and 2020. The Soil-Adjusted Vegetation Index (SAVI) values showed an extensive decline in surface permeability and the LST values showed an overall increase (from a maximum of 41 °C to 43 °C) of surface temperature in Tamil Nadu’s major cities with the highest upsurge for urban built-up areas between 2000 and 2020. Major cities built-up and non-vegetation areas in Tamil Nadu were depicted as potential drought hotspots. Our results deliver significant metrics for surface permeability, vegetation condition, surface temperature, and drought monitoring and urges the regional planning authorities to address the current status and social-ecological impact of landscape changes and to preserve ecosystem services.