In the modern era, chemotherapy, radiation therapy, biomarker testing, immunotherapy, sonodynamic therapy, hormone therapy, photothermal therapy, photodynamic therapy, and many more therapies are available for cancer. Photodynamic therapy (PDT) is a potential, innovative and non-invasive way of treating cancer. The main component of PDT is photosensitizers (PS), role in the practical applications of PDT. When these PS are exposed to appropriate light or laser irradiation, they absorb the energy and enter an excited state. They eventually transmit the energy to the neighbouring molecules, generating reactive oxygen species (ROS), especially singlet oxygen (1O2) into the model animals and patients. The most used and popular sensitizers, such as photofrin, hematoporphyrin (Hp), aminolevulinic acid (ALA), Porphyrin, and its derivatives, were developed regularly from first-generation to third-generation PS. After the second-generation PS highly focused on Porphyrin and its derivatives with modification and complexation to boost the efficiency of PDT against cancer cells. This review focuses on the PDT development of porphyrins with nanoparticles as third-generation PS with selectivity, toxicity and biocompatibility. In addition, porphyrin-based nanomedicines are discussed in terms of current challenges and future prospects.