Two-dimensional (2D) nanomaterials offer a transformative platform for photothermal therapy (PTT) due to their unique physicochemical properties and exceptional photothermal conversion efficiencies. This Minireview summarizes the photothermal mechanisms of common 2D nanomaterials and details their synthesis, surface modification, and optimization strategies. Recent advances leveraging 2D nanomaterials for enhanced PTT are highlighted, with particular emphasis on synergistic therapeutic modalities. Despite the significant potential of 2D nanomaterials in PTT, challenges persist, including scalable and reproducible manufacturing, precise targeted delivery, understanding of the underlying biological interactions, and comprehensive assessment of long-term biocompatibility and toxicity. Looking forward, emerging technologies such as machine learning are expected to play a crucial role in accelerating the design and optimization of 2D nanomaterials for PTT, enabling the prediction of optimal structures, properties, and therapeutic efficacy, and ultimately paving the way for personalized nanomedicine.