Dengue, a mosquito-borne viral disease, is experiencing its largest surge in history, driven by climate and demographic change. Expanding transmission has highlighted previously under-recognised populations at heightened risk of severe disease, including people with multimorbidity and immunosuppression, for whom live-attenuated vaccines are contraindicated or unlicensed. This evolving epidemiology underscores the urgent need for safe and effective treatments for dengue, particularly for those with complex risk profiles compounded by socio-economic disadvantage. We examine ethical, regulatory, and implementation considerations to support World Health Organization target product profile development for dengue therapeutics. Our analysis highlights the need for better characterisation of risk groups, including through enhanced surveillance; co-produced approaches for their inclusion in research prioritisation, trials, and care; and strategies to address key barriers to access for all, such as rapid diagnostics. This framework has the potential to inform equitable development and delivery of countermeasures for other infectious threats to global health.