In this study we develop an “inference modeling” approach to compare and analyze how different disciplines (economics, political science, and behavioral science/environmental psychology) estimate vulnerability to drought. It is thought that a better understanding of these differences can lead to a synthesis of insights from the different disciplines and eventually to more comprehensive assessments of vulnerability. The new methodology consists of (1) developing inference models whose variables and assertions incorporate qualitative knowledge about vulnerability, (2) converting qualitative model variables into quantitative indicators by using fuzzy set theory, (3) collecting data on the values of the indicators from case study regions, (4) inputting the regional data to the models and computing quantitative values for susceptibility. The methodology was applied to three case study regions (in India, Portugal and Russia) having a range of socio-economic and water stress conditions. In some cases the estimates of susceptibility were surprisingly similar, in others not, depending on the factors included in the disciplinary models and their relative weights. A new approach was also taken to testing vulnerability parameters by comparing estimated water stress against a data set of drought occurrences based on media analysis. The new methodologies developed in this paper provide a consistent basis for comparing differences between disciplinary perspectives, and for identifying the importance of the differences.