The cellular milieu in which malignant growths or cancer stem cells reside is known as the tumour microenvironment (TME). It is the consequence of the interactivity amongst malignant and non-malignant cells and directly affects cancer development and progression. Reactive oxygen species (ROS) are chemically reactive molecules that contain oxygen, they are generated because of numerous endogenous and external factors. Endogenous ROS produced from mitochondria is known to significantly increase intracellular oxidative stress. In addition to playing a key role in several biological processes both in healthy and malignant cells, ROS function as secondary messengers in cell signalling. At low to moderate concentrations, ROS serves as signalling transducers to promote cancer cell motility, invasion, angiogenesis, and treatment resistance. At high concentrations, ROS can induce oxidative stress, leading to DNA damage, lipid peroxidation and protein oxidation. These effects can result in cell death or trigger signalling pathways that lead to apoptosis. The creation of innovative therapies and cancer management techniques has been aided by a thorough understanding of the TME. At present, surgery, chemotherapy, and radiotherapy, occasionally in combination, are the most often used methods for tumour treatment. The current challenge that these therapies face is the lack of spatiotemporal application specifically at the lesion which results in toxic effects on healthy cells associated with off-target drug delivery and undesirably high doses. Nanotechnology can be used to specifically deliver various chemicals via nanocarriers to target tumour cells, thereby increasing the accumulation of ROS-inducing agents at the site of the tumour. Nanoparticles can be engineered to release ROS-inducing agents in a controlled manner to the TME that will in turn react with the ROS to either increase or decrease it, thereby improving antitumour efficiency. Nano-delivery systems such as liposomes, nanocapsules, solid lipid nanoparticles and nanostructured lipid carriers were explored for the up/down-regulation of ROS. This review will discuss the use of nanotechnology in targeting and altering the ROS in the TME.