The androgen receptor (AR) is pivotal in the biology of sex hormone-regulated malignancies, with prostate cancer (PC) the most affected tumor. AR signals control the growth, survival, and migration of cancer cells, and they regulate the activation of macrophages, a cell type pivotal to the tumor ecosystem. Intriguingly, CaMKK2 has recently been identified as both an important AR-regulated gene in the context of PC and as a critical regulator of macrophage activation. By contrast, CaMKK2 is barely detectable in normal prostate or immune cells that mediate the response against tumorigenesis. These novel findings suggest that CaMKK2 resides at a critical molecular node that shapes the cancer ecosystem, and identifies this kinase as a novel therapeutic target for sex hormone-regulated cancers.