Equitable and effective vaccine uptake is a key issue in addressing COVID-19. To achieve this, we must comprehensively characterize the context-specific socio-behavioralandstructural determinants of vaccine uptake. However, to quickly focus public health interventions, state agencies and planners often rely on already existing indexes of “vulnerability.” Many such “vulnerability indexes” exist and become benchmarks for targeting interventions in wide ranging scenarios, but they vary considerably in the factors and themes that they cover. Some are even uncritical of the use of the word “vulnerable,” which should take on different meanings in different contexts. The objective of this study is to compare four vulnerability indexes produced by private, federal, and state institutions to assess the application of these measures to the needs of the COVID-19 pandemic and other emergent crises. We focus on federal, state, and private industries’ vulnerability indexes for the Commonwealth of Virginia. Qualitative comparison is done by considering each index’s methodologies to see how and why they defined and measured “vulnerability.” We also quantitatively compare them using percent agreement and illustrate the overlaps in localities identified as among the most vulnerable on a choropleth map. Finally, we provide a short case study that explores vaccine uptake in the six localities that were identified by at least three indexes as most vulnerable, and six localities with very low vaccine coverage that were identified by two or fewer indexes as highly vulnerable. By comparing the methodologies and index (dis)agreements, we discuss the appropriateness of using pre-existing vulnerability indexes as a public health decision-making tool for emergent crises, using COVID-19 vaccine uptake as a case study. The inconsistencies reflected by these indexes show both the need for context-specific and time-sensitive data collection in public health and policy response, and a critical critique of measured “vulnerability.”