Human breast and prostate cancers are complex diseases caused by the progressive accumulation of gene mutations combined with epigenetic deregulation of critical genes and derangement of signaling pathways. Compelling evidence indicates that steroid hormones elicit non-genomic responses in cytoplasm of target cells. In this cellular location, steroid-coupled receptors recruit signaling effectors or scaffold proteins, thereafter activating multiple pathways leading to proliferation, survival, migration and invasiveness. Thus, the immediate challenge is the dissection of key upstream events regulating steroid response in target tissues to prevent progression and improve treatment of breast and prostate cancers. Progress in our understanding of the molecular mechanisms that play a master role in these cancers has strongly stimulated the search for specific inhibitors of key signaling molecules. This review aims to give an up-to-date report of the complex network regulating non-genomic action of steroid hormones in target cells. The final section highlights recent advances from our laboratory and future directions in alternative approaches for the treatment of breast and prostate cancers.