Benefiting　from　the　unique　properties　of　ionizing　radiation,　such　as　high　tissue　penetration,　spatiotemporal　resolution,　and　clinical　relevance　compared　with　other　external　stimuli,　radiotherapy-induced　drug　release　strategies　are　showing　great　promise　in　developing　effective　and　personalized　cancer　treatments.　However,　the　requirement　of　high　doses　of　X-ray　irradiation　to　break　chemical　bonds　for　drug　release　limits　the　application　of　radiotherapy-induced　prodrug　activation　in　clinics.　Recent　advances　in　nanomaterials　offer　a　promising　approach　for　radiotherapy　sensitization　as　well　as　integrating　multiple　modalities　for　improved　therapy　outcomes.　In　particular,　the　catalytic　radiosensitization　that　utilizes　electrons　and　energy　generated　by　nanomaterials　upon　X-ray　irradiation　has　demonstrated　excellent　potential　for　enhanced　radiotherapy.　In　this　Review,　we　summarize　the　design　principles　of　X-ray-responsive　chemical　bonds　for　controlled　drug　release,　strategies　for　catalytic　radiosensitization,　and　recent　progress　of　X-ray-responsive　nanoradiosensitizers　for　enhanced　radiotherapy　by　integration　with　chemotherapy,　chemodynamic　therapy,　photodynamic　therapy,　photothermal　therapy,　gas　therapy,　and　immunotherapy.　Finally,　we　discuss　the　challenges　of　X-ray-responsive　nanoradiosensitizers　heading　toward　possible　clinical　translation.　We　expect　that　emerging　strategies　based　on　radiotherapy-triggered　drug　release　will　facilitate　a　frontier　in　accurate　and　effective　cancer　therapy　in　the　near　future.　©　2025　American　Chemical　Society.