Metal-based anticancer drugs play a significant role in the treatment of cancer and have contributed remarkably to improving patient outcomes. Platinum-based anticancer drugs are potent against a variety of cancerous cells, but the lack of selectivity, solubility, and other side effects have prompted the development of new metallodrugs that differ from the stereotypical ones. The chemistry of vanadium (IV/V) and ruthenium(II) metal complexes comprising different types of O- and/or N- and/or S- donor ligands will be promising for developing advanced anticancer agents. In this regard, the design of complexes, their hydrolytic stability, transformation, and identification of species in aqueous medium, behavior under various physiological conditions, and mode of interaction with the biological systems need to be understood. In addition, the mechanism of action of the metallodrugs by which they induce cancer cell death such as apoptosis, mitochondria membrane potential (MMP), reactive oxygen species (ROS), DNA breaking, etc. needs to be investigated. The vanadium and ruthenium complexes have a good history of showing anticancer activity, so they should be subject to development using the new ligand system for further exploration. These observations have motivated me to focus on my thesis work, which comprises the design and synthesis of novel vanadium (IV/V) and ruthenium(II) metal complexes featuring O- and/or N- and/or S- donor ligands incorporating bio-active molecules in relation to their in vitro anticancer activity.