For decades, the formal metal addenda substitution in the matrix of bulk metal oxides has been a prolific strategy to develop numerous (non‐)stoichiometric all‐inorganic compounds with tunable electronic and magnetic properties, and broad technological applications. In contrast to bulk mixed‐metal oxides, the formal metal‐addenda substitution in their molecular equivalents typically leads to stoichiometrically precise mixed‐metal cluster formulations which retain the overall structural topology of the monometallic archetype, but exhibit pronounced differences in terms of reactivity and spectroscopic properties. These mixed‐metal molecular metal oxides often show complex configurational isomerism that has been the subject of many experimental and theoretical studies. The mixed‐addenda metal‐oxo clusters are most prominent among the classical plenary (that contain no vacant metal sites) polyoxometalate (POMs) archetypes, which have emerging applications in homogeneous catalysis and material science (e.g. formation of open frameworks), and have also been explored in heterogeneous metal organic framework (MOF) catalysts. Therefore, this article provides comprehensive theoretical and experimental insights into the isomer problem of mixed‐addenda molecular metal oxides and their applications.