Here, we fabricated two plasmonic 2D TiCT-based nanocomposites (Au/MXene and Au/FeO/MXene) with similarly high anti-cancer photothermal therapy (PTT) capabilities, but with less in vivo toxicity than a pure MXene. Au/MXene was synthesized by in situ reduction of tetrachloroauric acid using NaBH on TiCT flakes. For targeted PTT, magnetic Au/FeO/MXene was synthesized via a reaction between freshly prepared magnetite FeO NPs and MXene solution, followed by in situ integration of gold nanoparticles (AuNPs). Morphological characterization by XRD, SEM, and TEM revealed the successful synthesis of Au/MXene and Au/FeO/MXene. Both new composites exhibited a significant in vitro dose-dependent PTT effect against human breast cancer cells MCF7. Interestingly, in vivo acute toxicity assays using zebrafish embryos indicated that Au/MXene and Au/FeO/MXene had less embryonic mortality (LC ≫ 1000 µg/mL) than pure MXene (LC=257.46 µg/mL). Our new Au/MXene and Au/FeO/MXene nanocomposites could be safer and more suitable than the pure MXene for biomedical applications, especially when targeted PTT is warranted.