Metastasis is a complex process in which cancer cells migrate from the primary tumor, invade into the vasculature, and travel to distant parts of the body to establish secondary tumors. Cells with a greater metastatic potential have a proclivity for leading migration away from the primary tumor. Progress in identifying cells primed to metastasize and in assessing metastatic risk has been slow. This may be due in part to the lack of consistent molecular prognostic markers between cancer types and significant heterogeneity in metastatic potential within the tumor. Furthermore, not all tumors are metastatic and determining the metastatic proclivity of single tumor cells remains a major challenge. Another looming scientific question is estimating the metastatic “potential” because conventional techniques, e.g., Immunohistochemistry (IHC) are not capable of this and only molecular imaging can resolve these issues. So far, improved imaging platforms have helped detect established metastases and assessed tumor cell properties such as surrogate markers of metastatic potential. However, single cell-based assays to measure the dynamic pro-metastatic signaling programs that contribute to the 'potential' for metastasis remains a Holy Grail.