Distinctive optoelectronic properties of two-dimensional nanomaterials (2DNMs) offer unique opportunities in nanomedicine photothermal therapy. Highly tunable optical properties and high photothermal conversion efficiency in addition to the large surface area, biocompatibility, and versatile functionalization, make 2DNMs promising photothermal agents and potential for photothermal therapies (PTT). When exposed to near-infrared light, 2DNMs exhibit plasmonic effects and demonstrate excitonic transitions that favor the conversion of light energy into thermal energy with promising applications in PTT and multimodal therapeutics. In the pursuit of effective and versatile cancer treatment strategies, driven by the ever-growing demand for minimally invasive and targeted cancer treatment approaches, 2DNMs (e.g., graphene, transition-metal dichalcogenides, and MXenes) offer exceptional light-absorbing capabilities and highly tunable surface properties/functionalization, enabling precise control over their photothermal performance and biocompatibility. Moreover, their tunable electronic and optical properties make them versatile platforms for multimodal imaging and therapeutic applications. Despite some limitations, PTT has the potential to become a viable alternative to traditional therapies such as chemotherapy and surgery. In this review, we concisely highlight the opportunities and challenges associated with unique optical properties of 2DNMs, which may broaden our outlook on their engineered applications in nanomedicine. Moreover, the potential risks of uncontrolled heat generation and thermal damage to healthy tissues are discussed, highlighting the need for precise dosimetry and control mechanisms. In addition, issues, such as potential toxicity, stability in physiological conditions, low penetration depth, and challenges associated with large-scale production, are addressed to facilitate the successful clinical translation of 2DNMs.