Background <p>Dengue, a vector-borne disease caused by the dengue virus, has emerged as a global public health concern, given the tenfold rise in reported cases over the last two decades. In light of the upcoming dengue interventions, country-specific cost-of-illness estimates are required to evaluate the cost-effectiveness of new interventions against dengue. This study aims to conduct an updated systematic review of dengue cost-of-illness studies, extracting the relevant data, and conducting regression analysis to explore potential factors contributing to the cost variations among countries.</p> Methods <p>We used the MEDLINE, EMBASE, PubMed, and Web of Science databases to systematically search for published dengue cost-of-illness studies reporting primary data on costs per dengue episode. A descriptive analysis was conducted across all extracted studies. Linear regression analysis was performed to investigate the association between the GDP per capita and cost per episode. The quality of the included studies was also assessed.</p> Results <p>Fifty-six studies were included, of which 22 used the societal perspective. The reported total cost per episode ranged from $15.0 for outpatients in Burkina Faso to $9,386.1 for intensive care unit patients in Mexico. Linear regression analysis revealed that the cost of dengue illness varies significantly across countries and regions, and was positively related to the setting’s GDP per capita. The quality assessment demonstrated that improvements are needed in future studies, particularly in the reporting of the methodology.</p> Conclusions <p>Cost of dengue illness varies widely across countries and regions. Future research should focus on understanding other drivers of cost variations beyond GDP per capita to improve the cost estimates for economic evaluation studies. The results presented in this study can serve as crucial input parameters for future economic evaluations, supporting decision makers in allocating resources for dengue intervention programmes.</p>