The use of metal nanoparticles (M-NPs) in cancer therapy has gained significant consideration owing to their exceptional physical and chemical features. However, due to the limitations, such as specificity and toxicity towards healthy cells, their application in clinical translations has been restricted. Hyaluronic acid (HA), a biocompatible and biodegradable polysaccharide, has been extensively used as a targeting moiety, due to its ability to selectively bind to the CD44 receptors overexpressed on cancer cells. The HA-modified M-NPs have demonstrated promising results in improving specificity and efficacy in cancer therapy. This review discusses the significance of nanotechnology, the state of cancers, and the functions of HA-modified M-NPs, and other substituents in cancer therapy applications. Additionally, the role of various types of selected noble and non-noble M-NPs used in cancer therapy are described, along with the mechanisms involved in cancer targeting. Additionally, the purpose of HA, its sources and production processes, as well as its chemical and biological properties are described. In-depth explanations are provided about the contemporary applications of HA-modified noble and non-noble M-NPs and other substituents in cancer therapy. Furthermore, potential obstacles in optimizing HA-modified M-NPs, in terms of clinical translations, are discussed, followed by a conclusion and future prospects.