Cancer is a multifaceted disease that closes the curtains of life of infected individuals globally. By 2030, it is predicted that there will be a rise in new cancer cases and cancer deaths of up to 26 million and 17 million per year, respectively. Growing demand for chemotherapy over the past few years and a constrained supply of different anti-cancer drugs have ultimately driven up the price of various anticancerous drugs available in the clinical market. In order to address the widespread concerns about increasing cancer cases and the current costs of chemotherapy, researchers have explored extreme fungal diversity, which has significant source for the sustainable alternative production of anti-cancerous agents with higher yields, lower production costs, and less time consumption. In addition to extremophilic bacteria, which have been most extensively studied, extremophilic fungi are also ubiquitous but have received less attention in the past as a source of novel bioactive compounds. Along with the diversity of extremophilic fungi, endophytic fungi also hold out a new, hope for the eventual finding of cancer treatments. The major components of novel fungi exhibiting anti-cancerous effects are alkaloids, terpenoids, glycosides, saponin, peptides, steroids, phenols, quinones, and flavonoids. Therefore, the focus of the current review is on the reported anti-cancerous compounds produced by novel extremophilic and endophytic fungi, which offers a promising prospect for their bench-scale commercial production. The prospects and constraints for further clinical development along with the cost analysis of available commercial drugs in comparison to those derived from fungi also discussed.