Background <p>Chagas disease has historically been linked to triatomines and rural areas. However, urban infestations by one of its vectors, <i>Triatoma infestans</i>, are increasingly being reported. Urbanization is reshaping vectorial transmission patterns of this disease, creating new collective health challenges. To provide evidence on the eco-epidemiological status of Chagas in the metropolitan region of San Juan, Argentina, this study integrates data collected on biomedical, epidemiological, socioenvironmental, and territorial factors.</p> Methods <p>We conducted a cross-sectional analysis of 432 urban houses for infestations by <i>Triatoma infestans</i> and infection of these vectors with <i>Trypanosoma cruzi</i>, complemented by environmental, sociodemographic, and human practices surveys. Additionally, we carried out information, education, and communication (IEC) activities to engage with and become acquainted with the community. The IEC activities included immersive virtual reality experiences, community dialogue, and educational games in public spaces.</p> Results <p>Our study revealed a house infestation prevalence with <i>T. infestans</i> of 10% both indoors and in the houses’ outdoor spaces; <i>T. cruzi</i> infection was not detectable in any of the insects<i>.</i> Wind was identified as an environmental factor associated with house infestation, as was the presence of chicken coops, in addition to the condition of the houses (structural condition, such as cracks and poor plastering, and how the outdoor space of the houses was used, e.g., for the storage of objects that had accumulated over time). A combination of sociodemographic and environmental factors influenced <i>T. infestans</i> infestation prevalence. The IEC activities reached over 150 community members and promoted a dialogue about Chagas disease and vector control. The virtual reality and educational games encouraged strong youth engagement, and the media campaign helped raise awareness and visibility of the issue in the region.</p> Conclusions <p>The infestation prevalence of <i>T. infestans</i> in the urban area of San Juan highlights the need for urban-specific control strategies that differ from those used in rural settings. The key findings of this study, such as chicken coops being infestation hotspots and the importance of wind direction, and the unique urban context (high-density housing, a territorial institutional presence, and community networks), enable us to recognize opportunities for integrated, multi-actor control frameworks that actively involve communities.</p> Graphical Abstract <p></p>