<p>Photodynamic therapy (PDT) is an innovative and minimally invasive approach that has attracted considerable attention and interest in the medical community in recent years. The technique is primarily used to treat tumors and has received official approval for the management of several types of cancer. The process involves the injection of specialized light-sensitive materials into the body. Subsequently, when light of an optimal wavelength (the wavelength at which the photosensitizer is best absorbed and penetrates the tissue) is directed at these materials, it causes the production of reactive oxygen species. These reactive oxygen species play an important role in inducing cellular damage that ultimately leads to the death of cancer cells. Therefore, this treatment modality is based on three fundamental principles. This review comprehensively examines the fundamental principles governing PDT, with a specific focus on photosensitizer design, irradiation parameters, and tumor microenvironment oxygenation. A critical analysis of each component is provided, underscoring their collective importance in optimizing PDT efficacy for oncological applications. </p>