Infectious diseases of poverty (IDoP) affect disproportionately resource-limited and marginalized populations, resulting in spatial patterns of vulnerability across various geographical areas. Currently, no spatial indices exist to quantify vulnerability to IDoP at a fine geographical level within countries, such as municipalities or provinces. Without such an index, policymakers cannot effectively allocate resources or target interventions in the most vulnerable areas. This protocol aims to specify a methodological approach to measure spatial variation in vulnerability to IDoP. We will evaluate this methodological approach using surveillance and seroprevalence data from the Dominican Republic (DR) as part of a broader effort to develop a regional index for the Caribbean region. The study will consist of three main components. The first component involves identifying the relevant factors associated with IDoP in the Caribbean region through a scoping review, supplemented by expert-elicited opinion. The second component will apply a Fuzzy Analytic Hierarchy Process to weigh the aforementioned factors and develop a spatial composite index, using open data and available national surveys in the DR. In the final component, we will evaluate and validate the index by analysing the prevalence of at least three IDoPs at a fine-grained municipal level in the DR, using seroprevalence data from a 2021 national field study and other national surveillance programs. The spatial vulnerability index framework developed in this study will assess the degree of vulnerability to IDoP across different geographical scales, depending on data availability in each country.