AbstractLocal photothermal hyperthermia for tumor ablation and specific stimuliresponsive gas therapy feature the merits of remote operation, noninvasive intervention, and in situ tumor‐specific activation in cancer‐therapeutic biomedicine. Inspired by synergistic/sequential therapeutic modality, herein a novel therapeutic modality is reported based on the construction of two‐dimensional (2D) core/shell‐structured Nb2C–MSNs–SNO composite nanosheets for photonic thermogaseous therapy. A phototriggered thermogas‐generating nanoreactor is designed via mesoporous silica layer coating on the surface of Nb2C MXene nanosheets, where the mesopores provide the reservoirs for NO donor (S‐nitrosothiol (RSNO)), and the core of Nb2C produces heat shock upon second near‐infrared biowindow (NIR‐II) laser irradiation. The Nb2C–MSNs–SNO‐enabled photonic thermogaseous therapy undergoes a sequential process of phototriggered heat production from the core of Nb2C and thermotriggered NO generation, together with photoacoustic‐imaging (PAI) guidance and monitoring. The constructed Nb2C–MSNs–SNO nanoreactors exhibit high‐NIR‐induced photothermal effect, intense NIR‐controlled NO release, and desirable PAI performance. Based on these unique theranostic properties of Nb2C–MSNs–SNO nanocomposites, sequential photonic thermogaseous therapy with limited systematic toxicity on efficiently suppressing tumor growth is achieved by PAI‐guided NIR‐controlled NO release as well as heat generation. Such a thermogaseous approach representes a stimuli‐selective strategy for synergistic/sequential cancer treatment.