Recent increases in dengue cases across the region of the Americas have underscored the need for an integrated and collaborative One Health approach to address the potential of widespread autochthonous dengue in the continental USA. Improvements in the public health, social and health sectors are paramount in ensuring that communities are better protected. Furthermore, communities would benefit from effective adaptive strategies in the event of autochthonous dengue outbreaks. There is an opportunity to address existing challenges in the control of mosquitoes, public health infrastructure and funding that are necessary to recover from threats from climate-sensitive pathogens. Each component will improve preparedness toward widespread autochthonous dengue. This review provides an outline of adaptive and mitigating strategies and offers opportunities to address challenges through a One Health lens.