Metals are indispensable in the life of all organisms, in fact, their dysregulation causes various disorders caused by an interruption of their homeostasis. Nowadays different transition metals are incorporated into pharmaceutical products as diagnostic and therapeutic agents because of their electronic structure which gives them versatility in terms of tuning molecule properties, differently from organic molecules. Hence the interest in the study of metal-drug complexes from different points of view was born and many approaches were developed for the characterization, activation, delivery and molecular mechanisms clarification. The integration of these different approaches starting from chemoproteomics passing through nanoparticle systems to different activation strategies allows the understanding of the cellular responses of metallic drugs, which can be the basis for the design of new drugs and/or modification of drugs currently in use. This review aims to briefly summarize the recent advances in this area by describing the technological platforms and their possible applications to identify protein targets for discovering the mechanisms of action of metallodrugs, and to improve their efficiency in terms of administration.