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Singapore experiences endemic dengue. Vector control remains the primary means to reduce transmission due to the lack of available therapeutics. Resource limitations mean that vector-control tools need to be optimized, which can be achieved by studying risk factors related to disease transmission. We developed a statistical modelling framework which can account for a high-resolution and high-dimensional set of covariates to delineate spatio-temporal characteristics that are associated with dengue transmission from 2014 to 2020 in Singapore. We applied the proposed framework to two distinct datasets, stratified based on the primary type of housing within each spatial unit. Generalized additive models reveal non-linear exposure responses between a large range of ecological and anthropogenic factors as well as dengue incidence rates. At values below their mean, lesser mean total daily rainfall (Incidence rate ratio (IRR): 3.75, 95% CI: 1.00–14.05, Mean: 4.40 mm), decreased mean windspeed (IRR: 3.65, 95% CI: 1.87–7.10, Mean: 4.53 km/h), and lower building heights (IRR: 2.62, 95% CI: 1.44–4.77, Mean: 6.5 m) displayed positive associations, while higher than average annual NO2 concentrations (IRR: 0.35, 95% CI: 0.18–0.66, Mean: 13.8 ppb) were estimated to be negatively associated with dengue incidence rates. Our study provides an understanding of associations between ecological and anthropogenic characteristics with dengue transmission. These findings help us understand high-risk areas of dengue transmission, and allows for land-use planning and formulation of vector control policies. [ABSTRACT FROM AUTHOR]