Metastasis is a leading cause of cancer-associated deaths across several cancer types, yet the molecular details of its development have not been fully elucidated. Transcriptomic analysis can provide insight into the gene expression changes in the tumor that confer metastatic potential even during early stages of tumorigenesis. Here, by leveraging RNA-Seq data collected by The Cancer Genome Atlas (TCGA), we systematically identified mechanisms consistently associated with metastasis in primary tumors from 4844 patients across 13 different cancer types via comparison of primary tumors from patients with primary site, node-negative disease with no recorded distant metastasis (N0 not M1) compared to primary tumors from patients with node-positive disease (N1, N2, or N3). Differentially expressed genes were first determined within each cancer type, to reduce tissue- or disease-specific effects. Subsequently, via meta-analysis, we combine these results to identify commonality across 13 different types of cancer. Next, using a proprietary drug prediction algorithm called Drugfinder, we identified drug candidates that can target metastasis across all cancer types and within specific cancer types.