Pakistan remains a frequent victim of desertification. This study aims to conduct an assessment of desertification vulnerability and desertification degree of district Bahawalpur, Rahim Yar Khan and Rajanpur, South Punjab, Pakistan, for the period 2001-2018. The datasets of three sensors of MODIS, namely MOD13Q1, MOD11A2 and MOD16A2, with a spatial resolution of 25m, were acquired for 2001, 2009 and 2018, for the study area, from USGS. The assessment of desertification vulnerability has been done by calculating Normalized Difference Vegetation Index (NDVI), Soil Adjusted Vegetation Index (SAVI), Transformed Normalized Difference Vegetation Index (TNDVI), Moisture Stress Index (MSI), Potential Evapotranspiration (PET), Land Surface Temperature (LST) and Weighted Overlay analysis (WOL). The Desertification Difference Index (DDI) analysis concluded a 7.84% increase in area under vegetation and 7.74% decrease in barren land, from 2001 to 2018. However, a 6.87 rise in Max LST and a 3.06 rise in Min LST, from 2001-2018, left most of the increase in area under vegetation to be unhealthy, or dead. The Desertification Vulnerability Index (DVI) analysis presented an increase of 11.09% in the area covered by High desertification vulnerability category, i.e. from 7.4% in 2001 to 18.49% in 2018, whereas a 39.88% decrease was witnessed in the area covered by the Low desertification vulnerability category. An increase of 28.47% in the Medium desertification vulnerability category, in the study area was witnessed. Empirical support provided by the results, can help the future scientists and policy makers to work on mitigating this disaster to protect this climatically fragile region.