The vulnerability represents the level to which any ecosystem experiences impairment due to natural distress. One such distress is drought, a prolonged phase of deficient rainfall that causes the depletion of water resources. The possibility of the influences of drought principally depends on the vulnerability of the affected area. The predominantly arid climate of Pakistan and the dependence of its economy on agriculture make it vulnerable to climate change. Rahim Yar Khan and Tharparkar have similar environmental conditions, but Tharparkar experiences more droughts. Vulnerability factors observed by the two districts among the regions are different even with similar climate conditions. The system vulnerability to drought was observed for two districts by using the analytical hierarchy process (AHP) and drought vulnerability index (DVI). The drought vulnerability index (DVI) was used to assess the meteorological, agricultural, hydrological, and socio-economic indicators to build the hierarchy for these inconsistence factors and evaluate the most vulnerable and affecting cause among the meteorological, agricultural, hydrological, and socio-economic indicators. The selected measures specify the hypotheses and the relativity of the indicators to the overall vulnerability of the system. The evaluated weights for each variable are derived from the analytical hierarchy process by comparing the variables of the selected indicators. Due to different meteorological, agricultural, and socio-economic conditions, the weights for the DVI were not the same in both study districts, i.e., Rahim Yar Khan and Tharparkar. The classification of vulnerability depending upon the drought vulnerability index with AHP suggests that the DV indexation is favorable in assessing the regional drought vulnerability. The drought vulnerability assessment of Tharparkar indicates that Tharparkar is highly vulnerable to drought, i.e., DVI = 0.066, as it is highly dependent on irrigation resources for its agriculture and livestock. The unavailability of hydrological resources has increased the drought vulnerability of the Tharparkar, which corresponds to a high level of agricultural damage due to droughts. However, the district of Rahim Yar Khan with developed irrigation resources has a lower drought vulnerability index (DVI = 0.011). It is necessary for Tharparkar to establish countermeasures to mitigate the drought vulnerability through the development of water resources. Future studies are needed to be focused on more indicators for assessing particular drought vulnerability issues in order to reduce the drought vulnerability of Tharparkar.