Background: Cancer remains a leading cause of global mortality, accounting for approximately 10 million deaths in 2020 alone. Conventional therapies, including chemotherapy, radiotherapy, and surgery, are often plagued by systemic toxicity, poor pharmacokinetics, inadequate tumor selectivity, and multidrug resistance. Objective: This review comprehensively evaluates the mechanistic basis, therapeutic applications, and future prospects of nanoparticle (NP)-mediated drug delivery in oncology, with special emphasis on the integration of natural bioactive compounds within nanotechnology platforms. Methods: A synthesis of peer-reviewed literature was performed, drawing from two key review articles and their cited evidence base. Results: NPs confer a range of advantages including enhanced bioavailability, controlled drug release, passive and active tumor targeting via the enhanced permeability and retention (EPR) effect and receptor-mediated endocytosis, and the capacity for combination and gene therapy. Natural compounds—including anthocyanins, ellagic acid, resveratrol, and quercetin—demonstrate potent anticancer properties but are severely limited by poor aqueous solubility and rapid in vivo clearance; nano-encapsulation resolves many of these limitations.