Cancer presents a formidable challenge, necessitating innovative therapies that maximize effectiveness while minimizing harm to healthy tissues. Nanotechnology has emerged as a transformative force in cancer treatment, particularly through nano-enabled photodynamic therapy (NE-PDT), which leverages precise and targeted interventions. NE-PDT capitalizes on photosensitizers activated by light to generate reactive oxygen species (ROS) that initiate apoptotic pathways in cancer cells. Nanoparticle enhancements optimize this process, improving drug delivery, selectivity, and ROS production within tumors. This review dissects NE-PDT's mechanistic framework, showcasing its potential to harness apoptosis as a potent tool in cancer therapy. Furthermore, the review explores the synergy between NE-PDT and complementary treatments like chemotherapy, immunotherapy, and targeted therapies, highlighting the potential to amplify apoptotic responses, enhance immune recognition of cancer cells, and inhibit resistance mechanisms. Preclinical and clinical advancements in NE-PDT demonstrate its efficacy across various cancer types. Challenges in translating NE-PDT into clinical practice are also addressed, emphasizing the need for optimizing nanoparticle design, refining dosimetry, and ensuring long-term safety. Ultimately, NE-PDT represents a promising approach in cancer therapy, utilizing the intricate mechanisms of apoptosis to address therapeutic hurdles. The review underscores the importance of understanding the interplay between nanoparticles, ROS generation, and apoptotic pathways, contributing to a deeper comprehension of cancer biology and novel therapeutic strategies. As interdisciplinary collaborations continue to thrive, NE-PDT offers hope for effective and targeted cancer interventions, where apoptosis manipulation becomes central to conquering cancer. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.