AbstractForest decline events have increased worldwide over the last decades, being holm oak one of the tree species with the most worrying trends across Europe. Previous research identified drought and soil pathogens as the main causes behind holm oak decline. However, despite tree health loss is a multifactorial phenomenon where abiotic and biotic factors interact in time and space, there are some abiotic factors whose influence has been commonly overlooked. Here, we evaluate how land use (forests versus savannas), topography, and climate extremes jointly relate to spatiotemporal patterns of holm oak defoliation over almost three decades (1987-2014) in Spain, where holm oak represents the 25% of the national forested area. We found an increasing defoliation trend in 119 of the total 134 holm oak plots evaluated, being this increase rate significantly higher in forests compared to savannas. Moreover, we have detected that the interaction between topography and summer drought can explain trends of holm oak decline across the Mediterranean region. While a higher occurrence of dry summers increases defoliation trends in complex terrains where forests dominate, an inverse relationship was found at flatter terrains where savannas are located. Our results contribute to growing evidence of the influence of local topography, tightly linked to potential soil water availability, on forest functioning, as it can shape forest vulnerability against climate extremes. The present work could assist the identification of potential tree decline hotspots over the Mediterranean region. Moreover, our findings suggest that forest adaptive management will be key to guarantee the health and future stability of Mediterranean oak ecosystems, especially in the topographically more complex areas where tree vulnerability to climate extremes may be greater.