The mineral composition, pore structure, and wettability characteristics of sandstone uranium ore layers are modified by CO₂+O₂ interactions, directly influencing leaching efficiency. A sandstone-type uranium deposit in Inner Mongolia was investigated to characterize the evolution of mineral composition, structure, and wettability under different CO₂+O₂ phase states. X-ray diffraction (XRD), scanning electron microscope (SEM)/energy dispersive spectroscopy (EDS), low-temperature N₂ adsorption, and nuclear magnetic resonance (NMR) techniques were employed to analyze these changes. Results indicate that silicates, carbonates, and pyrite are significantly dissolved by CO₂+O₂, with dissolution most pronounced under supercritical conditions at a CO₂∶O₂ ratio of 2∶1, reducing mineral contents by 17.90%, 45.24%, and 98.57%, respectively. Dissolution-precipitation processes reconstruct the microscopic pore structure, enhancing pore connectivity and heterogeneity. A marked pore-expanding effect is observed, characterized by the transformation of micropores into mesopores and macropores and the expansion of small-medium pore throats into larger ones (1~25 μm), resulting in a porosity increase of 10.26%~43.05%. Under supercritical conditions at a CO₂∶O₂ ratio of 2∶1, macropore-throat volume increases by 48.09%, leading to improved pore connectivity, whereas at a CO₂∶O₂ ratio of 1∶2, enhanced precipitation under supercritical conditions results in a relatively smaller porosity increase. Following CO₂∶O₂ treatment, the average water contact angle increases from 42.15° to 57.90°~77.54°, accompanied by reduced surface tension, indicating a shift toward weak water-wet conditions. This wettability alteration is primarily controlled by feldspar and carbonate dissolution and macropore development. Reduced water wettability minimizes water retention in micropores and fractures, thereby facilitating leaching agent seepage and diffusion. The research reveals the influence of CO₂/O₂ ratio, phase state and action time on the composition, structure and wettability of sandstone-type uranium ore. It is clear that the modification effect is the best under the condition of supercritical high CO₂ ratio, which can provide theoretical support for the efficient development of CO₂+O₂ in-situ leaching of uranium.