The goal of this PhD project was to study the genetic architecture of pear resistance to two of its most significant diseases and pests, fire blight and psylla, which cause severe yield losses in all the main pear production regions worldwide. The development of new pear varieties with resistance against these two biotic stresses is of major interest for Integrated Pest Management. This project was designed in a joint collaboration among Fondazione Edmund Mach (Italy), Institut de Recherches en Horticulture et Semences (France) and Plant & Food Research (New-Zealand). The interspecific pear F1 progeny T003 x ‘Moonglow’ was developed with the purpose of cumulating resistances to fire blight and psylla deriving from Asian and European pear cultivars. Single nucleotide polymorphism (SNP) and simple sequence repeat (SSR)-based genetic maps were built for T003 and ‘Moonglow’. Quantitative Trait Loci (QTLs) were detected for the resistances, demonstrating their polygenic nature. Marker-assisted selection (MAS) can now be applied for these two traits. Furthermore, the segregating population exhibited genetic incompatibilities, and the genomic regions associated with hybrid necrosis were mapped for the first time in pear. Development of molecular markers linked to the lethal genes should allow breeders to avoid crosses leading to incompatible combinations that could affect the expression of important agronomic traits co-segregating with these genes.