Natural compounds originating from plants offer a wide range of pharmacological potential and have traditionally been used to treat a wide range of diseases including cancer. Tanshinone IIA (Tan IIA), a bioactive molecule found in the roots of the Traditional Chinese Medicine (TCM) herb Salvia miltiorrhiza, has been shown to have remarkable anticancer properties through several mechanisms, such as inhibition of tumor cell growth and proliferation, metastasis, invasion, and angiogenesis, as well as induction of apoptosis and autophagy. It has demonstrated excellent anticancer efficacy against cell lines from breast, cervical, colorectal, gastric, lung, and prostate cancer by modulating multiple signaling pathways including PI3K/Akt, JAK/STAT, IGF-1R, and Bcl-2-Caspase pathways. This review focuses on the role of Tan IIA in the treatment of various cancers, as well as the underlying molecular mechanisms.