Photodynamic therapy (PDT) is an approved and promising treatment approach that utilizes a photosensitizer (PS) to produce cytotoxic reactive oxygen species (ROS) through irradiation to achieve tumor noninvasive therapy. However, the limited singlet oxygen generation, the nonspecific uptake of PS in normal cells, and tumor hypoxia have become major challenges in conventional PDT, impeding its development and further clinical application. This review summarizes an overview of recent advances for the enhanced PDT. The development of PDT with innovative strategies, including molecular engineering and heavy atom-free photosensitizers is presented and future directions in this promising field are also provided. This review aims to highlight the recent advances in PDT and discuss the potential strategies that show promise in overcoming the challenges of PDT.