AbstractThe large‐dimensional and rigid ceramic bulks fabricated by high‐temperature solid‐phase reaction and sintering have never been considered for possibly entering and circulating within the blood vessels for biomedical applications, especially on combating cancer. Here, it is reported for the first time that MAX ceramic biomaterials exhibit unique functionalities for dual‐mode photoacoustic/computed tomography imaging and are highly effective for in vivo photothermal ablation of tumors upon being exfoliated into ultrathin nanosheets within atomic thickness (MXene). As a paradigm, 2D ultrathin tantalum carbide nanosheets (Ta4C3 MXenes) with nanosized lateral sizes are successfully synthesized based on a two‐step liquid exfoliation strategy of MAX phase Ta4AlC3 by combined hydrofluoric acid (HF) etching and probe sonication. The structural, electronic, and surface characteristics of the as‐exfoliated nanosheets are revealed by various characterizations combined with first‐principles calculations via density functional theory. Especially, the superior photothermal‐conversion performance (efficiency η of 44.7%) and in vitro/in vivo photothermal ablation of tumor by biocompatible soybean phospholipid‐modified Ta4C3 nanosheets are systematically revealed and demonstrated. Based on the large family members of MXenes, this work may offer a paradigm that MXenes can achieve the specific biomedical applications (here, theranostic) providing that their compositions and nanostructures are carefully tuned and optimized to meet the strict requirements of biomedicine.