Nitric oxide (NO) is a ubiquitous, water-soluble, free radical gas that plays a crucial role in various physiological and pathological processes. Over the past decades, NO has emerged as a molecule of interest in carcinogenesis and tumor growth progression. On the other hand, it also appears as a potential anti-oncogenic agent. Strategies for manipulating in vivo production and exogenous delivery of this molecule for therapeutic gain are being investigated. However, further validation and experimental/clinical trials are required to develop novel strategies based on NO for cancer treatment and prevention. On the other hand, NO mediates multiple physiological and pathophysiological processes in the cardiovascular system. Moreover, pharmacological compounds that release NO have been useful tools for evaluating the pivotal role of NO in cardiovascular physiology and therapeutics. This review discusses the actions of NO in cancer, and the different mechanisms by which NO acts in different cancers such as breast, cervical, gastric, colorectal, and head and neck cancers are addressed. It also offers an insight into the role of NO in the management of cardiovascular diseases.