Natural product-based nanoformulations are used for the treatment of various human diseases, such as cancer, one of the chief causes of death worldwide. Since ages, these products have been studied for their potential health benefits and have been used to treat several diseases including cancers of different organs. Various plant-based isolates, including alkaloids, flavonoids, terpenoids, and polyphenols, have been explored for their therapeutic potential. Phyto-molecules such as vinca alkaloids, curcumin, dihydroartemisinin, ellagic acid, epigallocatechin gallate, eugenol, gambogic acid, and ferulic acid have been well explored for their ability to harness their properties in preventing and managing cancer. These biologically active compounds possess anti-proliferative, chemopreventive, chemotherapeutic, antitumor, and other properties. Some potential moieties have been further modified to enhance their biological profiles with the help of nanoformulations. In the field of cancer treatment, many nano-drug delivery systems have received significant attention for delivering these naturally occurring plant entities. Formulations can be structurally and functionally modified for controlled or sustained drug release, alone or in combination with other chemotherapeutic agents, for targeted delivery, resulting in notable outcomes in cancer treatment. This provides several unique advantages for plant isolates, including easy modification, increased accessibility, unregulated penetration, bioavailability, and biocompatibility. Drug delivery systems using nanoformulations have numerous benefits in the treatment of cancer, including precise targeting, minimizing side effects, reducing toxicity and drug resistance. In this chapter, we discuss the nanoformulations of different natural compounds with proven antitumor activity and their mechanisms of action.