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Vector-borne diseases (VBDs) pose a significant public health challenge in Saudi Arabia, particularly in the Jazan region. This study aimed to assess the knowledge, attitudes, and practices regarding VBDs among the population of Jazan and to identify factors associated with these variables. A cross-sectional survey was conducted among 642 adult residents of Jazan using a convenience random sampling technique. The survey tool consisted of 6 domains: demographics, knowledge of VBDs, preventive practices, care-seeking behavior, knowledge of specific VBDs, and attitudes towards VBDs. Data were analyzed using descriptive statistics, chi-square tests, t tests, ANOVA, and multivariable logistic regression. The majority of participants (60.0%) had high knowledge scores, while (75.5%) and (77.7%) had high attitude and practice scores, respectively. However, knowledge gaps were identified in specific areas, such as the transmission of leishmaniasis and Rift Valley fever. Gender was a significant predictor of both knowledge and practice scores, with males having higher knowledge and females demonstrating higher levels of preventive practices. Age, education, income, and working status were also associated with knowledge scores. The findings highlight the need for targeted interventions and educational campaigns to address the identified gaps in knowledge, attitudes, and practices. Future research should focus on exploring the effectiveness of different intervention strategies and investigating the integration of VBD prevention and control measures into existing healthcare systems. By employing a multi-disciplinary approach, evidence-based strategies can be developed to prevent and control VBDs, ultimately improving public health outcomes in Jazan and other endemic regions worldwide., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)