INTRODUCTION: Invasive non-typhoidal Salmonella (iNTS) disease is a global health concern, particularly for sub-Saharan Africa. Despite high case fatality risks, there is no vaccine available against the disease. An obstacle to vaccine development is a lack of data on the economic burden of iNTS disease in many parts of the world. The main aim of the current study is to estimate the economic burden of iNTS disease in 123 countries. METHODS: Several multivariate regression models were parameterised with the data obtained from an existing systematic literature review on the economic burden of iNTS disease and all forms of NTS disease. Various model diagnostics were performed to validate the statistical significance of each model outcome, and the most suitable model was selected to predict costs in countries where no data points were available. RESULTS: A generalised linear model with gamma distribution with log link was chosen based on model diagnostics. While the average economic burden per iNTS disease episode ranged from US$341 in Africa to US$2194 in Europe, the total economic burden of iNTS disease was the highest in Africa due to the high burden of the disease in the region. CONCLUSION: The current study indicates that the economic burden of iNTS disease is substantial. Given the scarcity of field-based iNTS disease economic burden estimates, cost extrapolation through an econometric framework can be helpful for understanding the associated cost implications in a resource-limited setting and for informing the cost-effectiveness of public health interventions including future vaccination strategies.