OMICS analyses have the potential to greatly enhance our understanding of rejection and other processes in xenotransplantation. These approaches may therefore contribute to extending the survival time of xenotransplants. Initial OMICS studies in brain-dead patients following transplantation of pig kidneys or hearts revealed increased expression of genes associated with humoral immune responses. This included activation of monocytes, macrophages, and natural killer (NK) cells, as well as endothelial activation, complement activation, and T cell development. Such multimodal deep phenotyping has been proposed as a potential game-changer in the field of xenotransplantation. However, it is essential to consider that viral infections may significantly influence the results of these analyses. Viruses are known to alter gene expression patterns, not only within the immune system but also in endothelial cells and other tissue compartments. Depending on the type of virus, the immune response may either be stimulated—as the host reacts against the infection—or suppressed, in cases involving immunosuppressive viruses. Therefore, integration of comprehensive virus screening is essential in such studies.