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While early Photosensitizers (PS) have found their way to the clinic, research in the last two decades has led to the development of third\u2010generation PS, including photodynamic nanomedicine for improved tumor delivery and minimal systemic or phototoxicity. In terms of nanoparticle design for PDT, we are witnessing a shift from passive to active delivery for improved outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises of a complex and dynamic landscape with myriad potential targets for photodynamic nanocarriers that are surface\u2010modified with ligands. Herein, we review ways to improvise PDT by actively targeting nanoparticles (NPs) to intracellular organelles such as mitochondria or lysosomes and so forth, overcoming the limitations caused by PDT\u2010induced hypoxia, disrupting the blood vascular networks in tumor tissues\u2014vascular targeted PDT (VTP) and targeting immune cells for photoimmunotherapy. 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