Cities become mission-critical zones during pandemics and it is vital to develop a better understanding of the factors that are associated with infection levels. The COVID-19 pandemic has impacted many cities severely; however, there is significant variance in its impact across cities. Pandemic infection levels are associated with inherent features of cities (e.g., population size, density, mobility patterns, socioeconomic condition, and health & environment), which need to be better understood. Intuitively, the infection levels are expected to be higher in big urban agglomerations, but the measurable influence of a specific urban feature is unclear. The present study examines 41 variables and their potential influence on COVID-19 cases and fatalities. The study uses a multi-method approach to study the influence of variables, classified as demographic, socioeconomic, mobility and connectivity, urban form and density, and health and environment dimensions. This study develops an index dubbed the PVI-CI for classifying the pandemic vulnerability levels of cities, grouping them into five vulnerability classes, from very high to very low. Furthermore, clustering and outlier analysis provides insights on the spatial clustering of cities with high and low vulnerability scores. This study provides strategic insights into levels of influence of key variables upon the spread of infections as well as fatalities, along with an objective ranking for the vulnerability of cities. Thus it provides critical wisdom needed for urban healthcare policy and resource management. The pandemic vulnerability index calculation method and the process present a blueprint for the development of similar indices for cities in other countries, leading to a better understanding and improved pandemic management for urban areas and post-pandemic urban planning across the world.