Background Different regions in Taiwan have varying levels of dengue risk; however, the same prevention messages were implemented nationwide for a prolonged period. People in areas with different risk levels may perceive the disease risk differently, and these perceptions may be linked to message fatigue. Individuals experiencing high levels of message fatigue may engage in fewer preventive activities. Although message fatigue has been studied concerning many infectious diseases, it has not been extensively researched in the context of dengue. Moreover, previous studies primarily focused on the general population regardless of risk level or on high-risk populations, with few examining message fatigue across areas with varying risk levels. Therefore, this study aimed to identify distinct predictors of message fatigue across different dengue-risk areas in Taiwan. Methodology/Principal Findings The online questionnaire was adapted from the measurement developed by So et al., based on the conceptual definition of message fatigue. Message fatigue has two dimensions: message environment (ME) and audience response (AR). A negative binomial model was used to examine the association between the demographic variables (sex, residency, education, occupation, age, and income) and the perceived variables (perceived prevalence, perceived severity, and optimistic bias) with ME and AR separately. The results showed that in high dengue-risk areas, individuals with an education level of high school or below reported significantly higher levels of AR compared to those educated higher than high school (1.10, 95% CI = 1.01–1.21). In medium dengue-risk areas, individuals in the optimism group were 1.12 times more likely (95% CI = 1.01–1.25) to report higher levels of ME than those in the realistic group. In low dengue-risk areas, younger individuals, males, and those with a high-school education or below reported significantly higher levels of AR. Conclusions/Significance This study revealed that dengue-message fatigue is associated with different variables across varying risk areas. These findings could inform global health communication strategies by identifying key demographic and perception-based predictors of message fatigue, enabling more targeted and effective public health messaging in regions with differing risk levels.