Drought is one of the most acute environmental issues in the arid and semi-arid regions, especially under the impact of climate variability. This study aims to assess the impacts of climate-induced droughts on the health of the vegetation during the years 1991-2021 within the spatio-temporal Mirpurkhas Division of Sindh. The SPEI was conducted to determine the main drought years and the magnitude of drought occurrences, whereas satellite-based vegetation indices, Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), and Difference Vegetation Index (DVI) were used to describe the vegetation dynamics. The analysis has been carried out at four illustrative years that are chosen on a decadal basis, that being 1991, 2001, 2011, and 2021. The SPEI findings show the years 1991, 2001, and 2021 were established as severe drought years when the climatic water balance was negative. Although the year 2011 was not characterized as a severe year of drought according to SPEI, it was included so as to compare the post-drought vegetative responses as well as to obtain decadal compositions. In 1991 and 2001, there was significant stress, especially in the region of Tharparkar and southern Mirpurkhas, where most of the vegetation was sparse and degraded. Localized resilience manifested as moderate recovery in Umerkot and Sanghar in 2011. In 2021, there was a combination of recovery and ongoing stress, where moderate-vegetation-dense areas expanded in terms of moderate to dense vegetation, whereas Tharparkar continued being vulnerable. In general, the findings show a strong relationship between the severity of drought and vegetation degradation, and the process is determined by a combination of climatic factors and the given interventions by human beings towards the irrigation activities and the use of the land. Integrated application of SPEI, NDVI, EVI, and DVI offers in-depth knowledge regarding the effects of drought and vegetation dynamics to enable sustainable management of resources and climate adaptation plans in the region.