Recurrent outbreaks of zoonotic infectious diseases highlight the importance of considering the interconnections between human, animal, and environmental health in disease prevention and control. This has given rise to the concept of One Health, which recognizes the interconnectedness of between human and animal health within their ecosystems. As a contribution to the One Health approach, this study aims to develop an indicator system to model the facilitation of the spread of zoonotic diseases. Initially, a literature review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to identify relevant indicators related to One Health. The selected indicators focused on demographics, socioeconomic aspects, interactions between animal and human populations and water bodies, as well as environmental conditions related to air quality and climate. These indicators were characterized using values obtained from the literature or calculated through distance analysis, geoprocessing tasks, and other methods. Subsequently, Multi-Criteria Decision-Making (MCDM) techniques, specifically the Entropy and Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) methods, were utilized to combine the indicators and create a composite metric for assessing the spread of zoonotic diseases. The final indicators selected were then tested against recorded zoonoses in the Valencian Community (Spain) for 2021, and a strong positive correlation was identified. Therefore, the proposed indicator system can be valuable in guiding the development of planning strategies that align with the One Health principles. Based on the results achieved, such strategies may prioritize the preservation of natural landscape features to mitigate habitat encroachment, protect land and water resources, and attenuate extreme atmospheric conditions.