Aedes aegypti is a cosmopolitan vector for arboviruses dengue, Zika and chikungunya, disseminated in all Brazilian states. The Eco-Bio-Social (EBS) strategy is vital in Aedes aegypti control as it mobilizes stakeholders (government, professionals, society, and academics) to promote healthy environments. This paper describes the rationale and methods of expanding the EBS strategy for Aedes aegypti control in Fortaleza, Northeast Brazil. A cluster, non-randomized controlled clinical trial was developed to analyze the strategy’s effectiveness in vulnerable territories (high incidence of dengue and violent deaths; low HDI; substandard urban infrastructure, high population density, and water scarcity). We selected two intervention and two control groups, resulting in a sample of approximately 16,000 properties. The intervention consisted of environmental management by sealing large elevated water tanks, introduction of beta fish in waterholes, elimination of potential breeding sites, and mobilization and training of schoolchildren, endemic disease workers, health workers, social mobilizers, and community leaders; community surveillance of arboviruses; construction and validation of a booklet for the prevention of arboviruses in pregnant women. We analyzed the costs of arboviruses to government and households, the intervention cost-effectiveness, chikungunya’s chronicity, and acceptance, sustainability, and governance of vector control actions. The primary outcome (infestation) was analyzed using the house, container, and Breteau indices. We hope that this study will help us understand how to scale up strategies to fight Aedes aegypti in vulnerable areas.