Cancer remains a major cause of morbidity and mortality worldwide and is still challenging to modern medicine due to its complex nature and heterogeneity, which necessitates innovative therapeutic approaches in addition to the current therapeutic strategies, which can cause severe toxicity, including immunosuppression, bone marrow suppression, and gastrointestinal issues, and, in certain cases, become ineffective, leading to further proliferation, metastasis, emergence of resistance, and inflammatory responses. The utilization of medicinal plants can address these challenges by modulating multiple signaling pathways. However, the utilization of extracts derived from medicinal plants or phytochemicals does not guarantee successful drug delivery to the targeted site. This highlights the importance of amalgamating nanotechnology with medicinal plants or phytoconstituents. Medicinal-plant-derived nanoparticles can address the challenges of current therapeutic strategies by enhancing targeted delivery of medicines/phytoconstituents with better biocompatibility and pharmacokinetics, reduced toxicity, and the ability to target multiple pathways to reduce resistance. Despite promising results in vitro and in vivo, medicinal-plant-derived nanoparticles have more ways to clear all the phases of clinical trials and be introduced into the clinic as therapeutic/adjuvant drugs. This chapter focuses on an in-depth overview of medicinal-plant-derived nanoparticles, their development, novel nanocarrier strategies, the molecular mechanisms involved, such as apoptosis associated with reactive oxygen species (ROS), apoptotic gene upregulation, the modulation of various signaling pathways, and mitochondrial oxidative stress, and preclinical and clinical research on medicinal-plant-derived nanoparticles for the treatment of various cancers, various limitations, and challenges limiting their utilization and future perspectives.