The World Health Organization endorses the study of diseases from the perspective of the Determinants of Health (DH). DH are known as the circumstances in which people are born and raised, the environment in which they grow up and age and their lifestyle. The aim of this study is to analyze the spatial behavior of the prevalence of chronic obstructive pulmonary disease (COPD) and asthma in 2017 in Aragon, a Mediterranean region in Spain, using a DH approach. The methodological process entailed building a spatial database collating sociodemographic and climate indicators, and then evaluating the spatial variability of the relationships between DH indicators and disease prevalence by combining the Principal Component Analysis (PCA), Geographically Weighted Regression (GWR) models and cartographic design techniques. GWR evidences both global and spatially varying relationships, although each prevalence behaves differently. Asthma seems closely tied to local climate patterns whereas COPD is largely influenced by the built environment. Consequently, the socioeconomic and climatic contrasts characterizing the study area translate into several DH scenarios leading to situations vulnerable to the prevalence of asthma and COPD. This differential DH behavior detected by local regression models is relevant to guiding and refining public health decision-making.