Cancer prevention through dietary intervention utilizing bioactive natural compounds has garnered significant attention due to the therapeutic limitations of conventional cancer treatments. These plant-derived active compounds, including polyphenols, terpenoids, organosulfur compounds, bioactive peptides, and alkaloids, possess potent anticancer properties. This systemic review addresses a critical gap in the scientific literature by elucidating the precise multitargeted oncogenic regulatory mechanisms of these molecules. A comprehensive methodology was employed, involving a systematic literature search across major electronic databases (including PubMed, Web of Science, Embase, and SCOPUS) to identify relevant original peer-reviewed studies. The evidence gathered demonstrates that these active compounds deliver significant health benefits and protect cells by modulating crucial molecular targets involved in cell cycle regulation, apoptosis, oncogenic signaling, epigenetic control, angiogenesis, oxidative stress, and inflammation. Specifically, they operate via multi-targeted cascades, such as inhibiting the PI3K/Akt, NF-κB, and STAT3 pathways. To provide a clear structural overview, these active compounds are categorized comprehensively based on their botanical and structural origins, including spices, fruits, and rhizomes. However, despite their promising bioactivities, these compounds have not yet been fully translated into clinical therapy due to challenges such as low bioavailability, rapid metabolism, limited systematic exposure, and a lack of convincing evidence from large-scale clinical trials. Although most current evidence remains rooted in in vitro and experimental animal models, clinical validation through high-quality trials is still required. Ultimately, this review underscores the potential of these active compounds and highlights how advances in formulation and nano delivery strategies offer promising solutions for effective cancer prevention.