For oncology research, the tumor model selection is driven by the study objectives. Due to the cancer heterogeneity, different tumor models will be needed according to the development stages: target validation, proof of concept of target inhibition by a lead compound (small molecules or biotherapeutics), or candidate selection for further clinical development. In most of the cases, subcutaneous implantations of murine or human tumors are the best tools to address the preclinical questions helping to prepare the clinical development. Nevertheless, the development of more complex tumor models is also requested to answer more specific preclinical questions: either using surgical procedures to graft the tumor within a specific organ for evaluating specific tumor-stroma interactions, or using genetic engineered animals to mimic the different stages of the tumor development, or to humanize the target.