A targeted investment of $124 billion over five years will enable 196 countries to strengthen their core capacities across the World Health Organization (WHO)’s Joint External Evaluation (JEE) indicators. Writing in PLOS Global Public Health, experts at Resolve to Save Lives estimated the costs required to strengthen country-level health security and identified associated cost drivers. The cost of building public health capacity was estimated based on investments needed, per country, to progress towards “demonstrated capacity” across all WHO JEE indicators. Personnel costs, including skilled health, public health, and animal health workers, are the single most influential cost driver, comprising 66% of total costs. These findings provide cost estimates to inform ongoing health security financing discussions at the global level and highlight the significant need for sustainable financing mechanisms.