Urban dwellers are exposed to communicable diseases, such as influenza, in various urban spaces. Current disease models are able to predict health outcomes at the individual scale but are mostly validated at coarse scales due to the lack of fine-scaled ground truth data. Further, a large number of transmission-driving factors have been considered in these models. Because of the lack of individual-scaled validations, the effectiveness of factors at their intended scale is not substantiated. These gaps significantly undermine the efficacy of the models in assessing the vulnerability of individuals, communities, and urban society. The objectives of this study are twofold. First, we aim to model and, most importantly, validate influenza-like illness (ILI) symptoms at the individual scale based on four sets of transmission-driving factors pertinent to home–work space, service space, ambient environment, and demographics. The effort is supported by an ensemble approach. For the second objective, we investigate the effectiveness of the factor sets through an impact analysis. The validation accuracy reaches 73.2–95.1%. The validation substantiates the effectiveness of factors pertinent to urban spaces and unveils the underlying mechanism that connects urban spaces and population health. With more fine-scaled health data becoming available, the findings of this study may see increasing value in informing policies that improve population health and urban livability.