Although nature has evolved numerous enzymes that use metals as substrates, artificial catalytic transformations of transition metals are rarely explored in chemistry. Only a handful of examples are available in the literature where catalysis is exploited to convert metal precursors into added-value compounds. Nonetheless, such catalytic reactions toward metal-based substrates have widened the toolbox of inorganic chemists to modify the coordination sphere of the metal centers or to enable new routes in light-driven organic synthesis. Furthermore, catalysis has been adopted to efficiently generate and deliver metallodrugs to different biological contexts. This perspective describes the novel synthetic paths and reactivities unlocked by catalytic transformations of metal-containing substrates and highlights the opportunities and challenges for the implementation of this approach to technological applications (i.e., chemical manufacturing and biomedicine).