The ubiquitous cytokine transforming growth factor-beta1 (TGF-beta1) is one of the most potent metastatic inducers. Functional interactomic mapping using high-throughput proteomic and genomic data provides valuable insights into the regulation of tumor suppressive and metastatic attributes of TGF-beta1. Polarity changes of the TGF-beta1 interactome at a given time contributes to these contrasting effects. Differential expression profiles of pivotal interactomic nodes contribute to these polarity changes. These insights are of immense value in the development of effective cancer therapeutics. Moreover, TGF-beta1 interactomic nodes are useful in discovering novel cancer biomarkers. This review describes an initial version of the TGF-beta1 interactome in relation to tumor progression and metastasis. Thus, this review embodies an important step towards the mapping of comprehensive and individualized TGF-beta1 interactomes that will assist in the development of personalized cancer therapeutics.