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Abstract Hypoxia is considered as a key microenvironmental feature of solid tumors. Luminescent transition metal complexes particularly those based on iridium and ruthenium have shown remarkable potentials for constructing sensitive oxygen‐sensing probes due to their unique oxygen quenching pathway. However, the low aqueous solubility of these complexes largely retards their sensing applications in biological media. Moreover, it remains difficult so far to use the existing complexes typically possessing only one luminescent domain to quantitatively detect the intratumoral hypoxia degree. Herein, an Ir(III) complex showing red emissions is designed and synthesized, and innovatively encapsulated within a hydrophobic pocket of Cyanine7‐modified cyclodextrin. The Ir(III) complex enables the oxygen detection, while the cyclodextrin is used not only for improving the water solubility and suppressing the luminescence quenching effect of the surrounding aqueous media, but also for carrying Cyanine7 to establish a ratiometric oxygen fluorescence probe. 2D nuclear magnetic resonance is carried out to confirm the host–guest structure. The oxygen‐responsive ability of the resulting ratiometric probe is evaluated through in vitro cell and multicellular experiments. Further animal studies about tumor oxygen level mapping demonstrate that the probe can be successfully used for quantitatively visualizing tumor hypoxia in vivo.