Cancer continues to be a leading cause of death globally, prompting the need for effective and less toxic therapies. Medicinal plants, with their diverse chemical compositions and biological activities, have emerged as promising candidates for cancer treatment. Recent research indicates that combining natural compounds with standard chemotherapeutic drugs can enhance their therapeutic effectiveness while reducing side effects. Preclinical and clinical trials have shown that the synergistic effects of medicinal plants and chemotherapy drugs can enhance anticancer treatment efficacy, while overcoming drug resistance mechanisms and reducing side effects like nausea and fatigue. Advances in drug delivery systems, such as nano-drug delivery systems, have improved the stability, bioavailability, and target-specific activity of natural bioactive compounds. Developments such as liposomes, nanoparticles, and micelles enable targeted delivery to tumor sites, reducing side effects and enhancing therapeutic efficacy. However, challenges remain in large-scale production, stability, physiological barriers, and regulatory issues. The development of natural product-based hybrids, such as antibody-drug conjugates (ADCs), proteolysis-targeting chimeras (PROTACs), and autophagy-targeting chimeras (AUTOTACs), has revolutionized cancer therapy by combining the therapeutic benefits of natural compounds with innovative drug delivery systems. These advancements hold great promise for personalized, less toxic cancer therapies, providing a more patient-centered approach. Ongoing research is crucial to overcoming challenges and moving these innovations from the lab to clinical application, offering hope for improved patient outcomes and quality of life in cancer care.