The assessment and identification of risk/vulnerable groups and risk factors are vital elements that can help quantify the pandemic potential of the SARS-CoV-2 virus in order to plan prevention and treatment measures. The aim of the study is to identify a methodological approach of population vulnerability to the SARS-CoV-2 virus infection. The study identifies reliable data sources and sets up a unitary database with statistical variables, quantitative and qualitative indicators with potential for being updated and improved. The analysis takes into account a number of variables/indicators (e.g., elderly persons, population without physician care, number of people suffering from cardiovascular diseases, number of people suffering from respiratory diseases, dwellings not connected to the public water supply network, no. of medical staff, number of COVID-19 hospitals, PCR testing laboratories, number of vaccinated persons) grouped into the key vulnerability components: exposure, sensitivity, coping capacity and adaptive capacity. They allowed the computation of the final Index of Population Vulnerability to the SARS-CoV-2 virus infection and the mapping of different dimensions of vulnerability. The study was performed using the statistical data available at NUTS3/County level provided by different institutions (e.g., the Ministry of Health, the National Institute of Public Health, the Strategic Communication Group, the National Institute of Statistics). The mapping of the different degrees of vulnerability could solve a problem of visibility for possible areas with vulnerable population, but also a problem of communication between different institutional health and administrative levels, as well as between all of them and the local communities and/or professionals.