Dengue fever remains one of the most pressing global public health challenges, driven by its increasing incidence, expanding geographical reach, and complex clinical manifestations. This review synthesises current knowledge on dengue’s epidemiology, transmission dynamics, and clinical spectrum, highlighting the roles of Aedes mosquitoes, environmental factors, and socioeconomic determinants in shaping disease patterns. We explore the immune-mediated mechanisms underlying severe dengue as well as emerging insights into epigenetic modifications that affect both acute and long-term outcomes. The multifaceted impact of dengue is further underscored by its occupational, maternal, and neonatal health complications, which contribute substantially to the economic and healthcare burdens in endemic regions. Innovative therapeutic strategies, including the development of monoclonal antibodies and novel vaccines, alongside integrated vector control and early warning systems, are advancing the fight against dengue. Future research directions and policy recommendations emphasises the need for affordable diagnostics, refined prognostic biomarkers, improved surveillance, and climate-adapted public health interventions to mitigate dengue’s spread and severity. Urban planning, though underexplored, has transformative potential in mitigating dengue through mosquito-resistant infrastructure and climate-adaptive strategies. Future efforts must integrate interdisciplinary solutions focusing on innovative therapeutics, targeted prevention, and strengthened healthcare systems to combat dengue effectively and address its evolving challenges in both endemic and emerging regions. © 2025 Elsevier B.V., All rights reserved.