Cities spend millions of dollars on rodent mitigation to reduce public health risks. Despite these efforts, infestations often remain high. Rodents thrive in the built environment in part due to reduced natural predators and the exploitation of garbage. Though sanitation and greenspace are important factors in rodent mitigation, more complex governance and action are needed. Urban rodents are dynamic and commensal in nature, so understanding the influence of prolific urban features, like building attributes, warrants scrutiny and additionally intersects mitigation strategies with stakeholders at a localized level. Here, we model how residential structures’ efficiency influences urban rodent populations. To do so, we created an agent-based model using characteristics of urban brown rats and their natural predator, red foxes, based on three distinct neighborhoods in Philadelphia, Pennsylvania. We varied whether retrofitting occurred and its duration as well as the percent of initial energy-efficient homes in each neighborhood. We found that initial housing conditions, retrofitting, and the duration of retrofitting all significantly reduced final rodent populations. However, retrofitting was most effective in reducing rodent populations in neighborhoods with extensive park access and low commercial activity. Additionally, across neighborhoods, single large efficiency initiatives showed greater potential for rodent reduction. Lastly, we show that the costs of large-scale retrofitting schemes are comparable to ten-year public health spending, demonstrating that retrofitting may have the potential to offset near-term costs. Our results showcase how system-view investments in integrated pest management can lead to sustained rodent pest mitigation and advance sustainable development goals, infrastructure innovation (Goal #9), reduced inequalities (Goal #10), and sustainable cities and communities (Goal #11).