Climatic scenario predicted for Mediterranean areas poses specific challenges for agricultural productions. The vulnerability of agricultural sectors to the modification of agro-climatic conditions depends on both the expected regional climate change and the sectors’ ability to adapt. For their perennial status, fruit tree crops are particularly exposed to environmental change. The quality and quantity of fruit productions are strongly affected by Genotype x Environment interactions. The overarching goal of MEDPOME-STONE is to explore wild pear and almond biodiversity and to select genotypes with enhanced resilience to climate change to promote long-term breeding and more sustainable production in new biodiversity-based crop systems. The project proposes to obtain the most detailed characterization of some wild pear and almond genetic diversity in the Mediterranean area, identifying variants associated with desired rootstocks traits to climate change resilience. By involving local farmers and stakeholders through a multi-actor approach, MEDPOME-STONE will valorize local knowledge and maximize the socioeconomic impact of its outcomes. To achieve the overarching goal, the MEDPOME-STONE consortium will work on three different scientific objectives: a) to valorize genetic diversity on local collections from Turkey, Italy, and Spain to reduce genetic erosion in wild pear and almond; b) the selection of plants adapted to increased drought conditions; c) the identification of molecular markers linked to drought tolerance. These three objectives will lead to (i) a more precise knowledge on the genetic diversity within accessions in the Mediterranean region; (ii) a more sustainable production promoting new biodiversity-based crop systems; (iii) novel breeding tools for marker-assisted selection (MAS) of varieties showing characteristics of improved adaptation to drought. A major strength of MEDPOME-STONE is the availability of large germplasm collections, some in multiple locations, covering a range of Mediterranean cultivation environments. The project partnership includes geneticists, breeders, and physiologists, that possess complementary expertise and will share knowledge, and define priority areas for research and breeding activities through the engagement of stakeholders and end-users.