Metastasis is the main cause of cancer-related death. It is surprising then that the exact nature of metastasis—the process by which cancer cells leave the primary tumor to reach distant organs, and resume proliferation—is not fully understood. Moreover, the different conditions under which the immune system can either promote or suppress metastasis are only now beginning to be uncovered. In recent years, our understanding of metastasis as a genocentric, cell-autonomous process has shifted toward a systemic model in which interactions between cancer cells and their surrounding microenvironments lead to dissemination and metastasis. In silico modeling of the various steps involved in metastasis can help provide an understanding of how tumor properties emerge from the complex interplays between tumor cells and their microenvironment. In silico models can also be useful in identifying the selective forces that favor the outcomes of cancer cells with metastatic potential.