Systematic treatment and cocktailed drug applications have become a paradigm shift for cancer therapy. This study aims to explore the highly potent herbal cocktail strategies and pharmacological mechanisms, by which herbal medicines are effective in cancer treatment. A total of 397 cases of clinically reported cancer treatments with pure herbs were scrutinized, and the herbal prescription rules were systematically analyzed. The core prescriptions and their pharmacological mechanisms were revealed. The results unveiled specific rules for effective herbal treatment of cancer, including boosting energy metabolism, inhibiting tumor proliferation, improving digestion and defecation, enhancing blood circulation, promoting gas exchange, and facilitating water and toxic substance metabolism. Pharmacologically, anti-cancer effects are achieved through the manipulation of PI3K-Akt, IL-17, HIF-1, VEGF, TNF, Wnt, and other pathways. Following this unfolded integrative prescription rule, herbal therapy demonstrated remarkable effects in clinical practices, from which a few representative cases are presented herein.