Over the past decade, metal complexes based on N-heterocyclic carbenes (NHCs) attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In addition to their well-known unlimited potential in several areas of the materials field and their use as highly efficient catalysts, more recently silver derivatives were employed as antimicrobial agents, while gold complexes were the focus of research efforts for the development of new anticancer compounds. Interesting literature data and recent results obtained from some of us reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. Particularly, some of these complexes were more active towards some cell lines belonging to breast cancer, which represents the primary cause of death among young women. Considering these evidences, new Au and Ag NHC complexes were prepared in order to improve their solubility and biological activity. Among the new Au NHC compounds, 1 and 11 showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the human topoisomerases I and II, essential enzymes involved in DNA metabolism and replication.