Cancer remains a leading cause of mortality worldwide, with dysregulated signaling pathways contributing significantly to tumor initiation, progression, metastasis, and therapeutic resistance. Aberrant activation of critical molecular cascades including the phosphoinositide 3-kinase/protein kinase B pathway, mitogen-activated protein kinase pathway, Wnt/β-catenin pathway, and nuclear factor-kappa B pathway drives oncogenic transformation and sustains malignant phenotypes across diverse cancer types. Plant-derived bioactive compounds have emerged as promising therapeutic agents capable of modulating these pathways through multifaceted molecular mechanisms. This review comprehensively examines the anticancer potential of major phytochemicals including curcumin, resveratrol, epigallocatechin gallate, quercetin, genistein, and other polyphenolic compounds, exploring their capacity to induce apoptosis, promote cell cycle arrest, inhibit angiogenesis, and suppress metastatic potential. We critically analyze preclinical evidence from in vitro and in vivo models demonstrating the efficacy of these compounds in targeting specific molecular nodes within dysregulated signaling networks. Furthermore, we evaluate clinical studies and translational insights that highlight both the therapeutic promise and challenges associated with plant-derived anticancer agents. The synergistic potential of combinatorial strategies integrating phytochemicals with conventional chemotherapy, radiotherapy, and targeted therapies is discussed in the context of enhanced efficacy and reduced toxicity. Finally, we address pharmacokinetic limitations, bioavailability concerns, regulatory considerations, and future directions toward the development of precision oncology approaches utilizing plant-derived compounds as standardized, evidence-based therapeutic interventions in translational medicine.