Human-wildlife interactions (HWI) are one of the most highly studied topics from the fields of wildlife management and are reported to be increasing globally as anthropogenic lands uses expand into wild lands, especially in mountainous areas where forest habitats are in the proximity of human settlements. The upper Prahova Valley in south-central Romania provides habitat to several native charismatic wildlife species. Since 1990 this area has become a major tourist destination now characterized by a high density of major transport infrastructures and homes. To assess how the changes in land use have affected HWIs, from September 2018 to August 2019, we discussed with 370 local citizens from the cities of Sinaia, Bușteni and Predeal. We developed maps of wildlife habitat fragmentation and connectivity and superimposed them over the locations with the HWI hotspots. According to the results, over 50% of the hotspots identified where located in areas exhibiting the greatest level of fragmentation, and the species frequently involved in interactions were the brown bear (Ursus arctos), wild boar (Sus scrofa), and red fox (Vulpes vulpes). The maps suggest that habitat fragmentation could represent a primal cause for the regions’ high frequency of animal descents into settlements, since wildlife habitats and ecological corridors are affected by the fragmentation of anthropogenic infrastructures especially in the proximity of major settlements. As a conclusion, our results highlight the need for sustainable landscape planning in order to optimize biodiversity management and diminish interactions between humans and wild animals, based on: a) mapping the areas characterized by high quality wildlife habitats and including them into a system of strict protection, b) developing or enhancing wildlife ecological corridors to favour animal movement between intact ecosystems, and c) regulating the expansion of human infrastructures in the proximity of strictly protected habitats.