The sedentary root-knot nematode Meloidogyne incognita is a widely distributed and highly polyphagous phytopathogen, which causes annual losses in the order of millions of dollars in damage to crops. M. incognita juveniles initiate the development of a permanent feeding site consisting of so-called giant cells. The elaborate changes in plant roots leading to the formation of giant cells are orchestrated by effectors in secretions of M. incognita. This thesis addresses the central hypothesis that genome diversity can be used for identifying key factors underlying both nematode virulence and host susceptibility. First, it describes the identification of the effector MiMSP32 based on positive, diversifying selection in the M. incognita genome. Further functional characterization of MiMSP32 in planta showed that it is indeed an important effector with a key role in nematode virulence. One of the host factors targeted by MiMSP32 in plants has a major impact on plant susceptibility to M. incognita. In complementary approach, this thesis also showed that genome diversity in a collection of 156 domesticated tomato lines without known major R-genes can be used to identify key host factors in susceptibility to M. incognita. Significant quantitative variation in tomato susceptibility was linked to genomic regions of these tomato lines using genome-wide association, resulting in a catalogue of genes associated with tomato susceptibility to M. incognita. Integration of genome diversity of both nematode and host could be used in future studies to formulate more efficient plant protection strategies.