Mild photothermal therapy (MPTT) generates therapeutic effect at the temperature below 45 ℃, which has the advantages of controllable treatment efficacy, reduced drug dosage, lower hyperthermia temperatures, and minimize damage to healthy tissues. MPTT can kill tumor cells at lower temperatures by blocking heat shock proteins (HSPs) expression without harming nearby healthy cells. Despite significant progress in MPTT, it remains primarily in the stages of basic and clinical research and has not yet seen widespread clinical adoption due to several technical challenges. In this review, we provide a comprehensive overview of the recent development of MPTT, emphasizing its anti-tumor mechanisms, the characteristics of commonly used photothermal agents (PTAs), and their biomedical applications. Specifically, we address the key obstacles facing MPTT and propose potential solutions, and explore the status of MPTT combined with other anti-tumor therapies and discuss its broader applications in areas such as anti-infection, obesity treatment, and vascular disease treatment. Finally, we look ahead to future research directions in MPTT, aiming to further enhance its efficiency and safety while developing new strategies for high-efficiency MPTT.