Metal-organic framework (MOF)-based materials are recognized as potential media for photo-reductive demineralization of heavy and radioactive metal(loid) pollutants. In this review, the recent progress achieved in the development of MOF-based photocatalysts is highlighted for the photocatalytic reduction of Cr(VI)) and U(VI) metal(loid)s in water based on three key performance metrics such as quantum yield (QE), space–time yield (STY), and figures of merit (FOMs). For such evaluation, particular emphasis has been placed on the effect of modification strategies and inorganic nodes (e.g., Zn, Ti, Zr, Fe, In, Cd, and Cr metal sites). Among the surveyed MOFs, flower-like Zn-MOF/[email protected] nanotube/[email protected]3PO4@MIL-125-NH2 and MOF-derived g-C3N4 nanosheets were identified as the best performers to detoxify chromium and uranium, respectively. The superiority of these MOF-photocatalysts is attributable to their superior capabilities for photoreduction process (e.g., in terms of electron-hole pair separation mechanisms, metals adsorption, and UV-visible light harvesting). The overall results of this review will help open a new room for the development of the next-generation MOF-based photocatalytic systems (in terms of catalytic activity, upscalability, and photocatalytic stability/reusability) for the efficient reduction of heavy and radioactive metal ions in water under solar light.