Reactive oxygen species (ROS) play a vital role in the biological process. Interestingly, based on the concentration of the ROS level, they can be beneficial or detrimental to tumor cell growth. Induction of disproportionality in the redox homeostasis by increased accumulation of free radicals, predominantly ROS, can assist cancer treatment. The elevated level of ROS inside the tumor damages the vital biomolecules of tumor cells, such as proteins, lipids, and nucleic acids. Hence, fine-tuning the ROS level in the tumor cells by novel therapeutics can help in the overproduction of ROS, and this further helps in ROS-induced apoptotic signaling. The present review discusses the role of ROS in cancer cells, their mechanism of action in cancer cell death, and the challenges associated with ROS therapy. The mechanisms of ROS generation by nanogenerators were also discussed. Furthermore, this review also explicates various ROS nanogenerators for selective generation and accumulation of ROS in tumor tissue for achieving higher anticancer activity.