Cancer is one of the most important healthcare matters, with the worst prognosis but the best possibilities for scientific development. It is likely to increase in the future and cause global havoc designating it as an epidemic. Cancer development requires urgent intervention. Past few decades have witnessed extensive research to challenge carcinogenesis. Treatment involving synthetic discipline is often associated with severe adverse effects, or even worsened prognosis. Accordingly, newer economic and patient friendly molecules are warranted. Many natural substances have proved their potential so far. Cucurbitacin B against cancer and other diseases has achieved towering popularity among the researchers around the world, as detailed in the below sections with summarized tables. In line with the fascinating role of cucurbitacin B against various types of cancers, through various molecular signaling pathways, it is justifiable to propose cucurbitacin B as a mainline chemotherapy before the onset and after the diagnosis of cancer.