Metastasis occurs when the most aggressive tumor cells disseminate and grow in other organs. The immune system is our major defense against cancer, as it recognizes malignant cells being capable to eliminate them. However, the most aggressive tumor cells can hijack the immune system and remain hidden from their surveillance. Based on the immune cell heterogeneity found across organs and metastatic clonal selection in given tissues, we hypothesize that the dynamic co-evolution in tumor and immune systems determine the occurrence of metastasis. To study these spatiotemporal dynamics of metastasis, we will use innovative tools to follow the chronological co-evolution of immune and cancer cells. Understanding co-evolving mechanisms will unveil fundamental knowledge of metastasis and new opportunities for therapy.