Niobium‐based MXenes exhibitefficient near‐infrared (NIR) absorption but remain underexplored for in vivo cancer therapy. In this study, we investigated Nb ₄ C ₃ T _x MXene as an NIR‐II photothermal therapy (PTT) sensitizer for melanoma. Both in vitro and in vivo experiments were performed using Nb ₄ C ₃ T _x in combination with pulsed 1064 nm laser irradiation. Tumor growth, histological changes, and spatial localization of MXene were assessed to evaluate therapeutic efficacy and safety. Nb ₄ C ₃ T _x significantly enhanced tumor suppression under pulsed NIR‐II irradiation, inducing extensive destruction of melanoma cells while sparing surrounding tissue. Histological analysis revealed macrophage‐mediated uptake and clearance of MXene, with no evidence of persistent accumulation in tumor remnants or visceral organs. Pulsed laser irradiation provided precise and rapid heating, improving treatment accuracy and minimizing collateral damage. However, complete tumor eradication was not achieved, likely owing to limited light penetration in bulky tumors and the nontargeted distribution of pristine MXene. Our study demonstrates the feasibility and safety of Nb ₄ C ₃ T _x MXene‐assisted PTT in vivo, providing the first experimental evidence of its therapeutic potential in melanoma treatment. These findings establish Nb ₄ C ₃ T _x as a promising platform for pulsed laser–mediated PTT, while highlighting the need for targeted functionalization and treatment optimization to achieve selective tumor ablation.

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