Metal–organic frameworks (MOFs), formed by the coordination of metal nodes and organic linkers, constitute a class of multifunctional materials with unprecedentedly high chemical/structural designability. Through properly harnessing the synergistic interplay between high atomic number nodes and functional linkers, radiation‐responsive MOFs have recently come on the scene, which can convert ionizing radiations (e.g., X‐ray, γ‐ray, β‐ray, α‐particle, and neutron) into electrical charges or visible light. Given the attributes of cost‐effectiveness, robust environmental stability, extensive chemical tunability, and diverse functionalities, cutting‐edge radiation‐responsive MOFs with remarkable electronic and optical properties have emerged as promising substitutes for conventional organic and inorganic radiation‐responsive substances in applications across biomedicine and technology. This review article documents recent advancements in radiation‐responsive MOFs by elucidating the foundational mechanisms governing electronic transport and photon conversion within frameworks through inherent node–linker and host–guest interactions prompted by high‐energy radiation. Furthermore, this review delves into state‐of‐the‐art applications that leverage newly formulated radiation‐responsive MOFs, capitalizing on precisely engineered component interactions to achieve efficient energy absorption, conversion, and emission. The rationale behind these developments is concluded and future opportunities for expanding the research of radiation‐responsive MOFs are simultaneously highlighted.