At the nexus of conventional medicine and contemporary pharmacological science, the therapeutic potential of phytochemicals in oncology offers a complicated paradigm. Current research on safety limits, pathological factors, and legal frameworks controlling phytochemical interventions in cancer treatment is summarized in this thorough review. Recent developments in bioavailability-enhancing technology and analytical chemistry have clarified essential elements influencing these substances’ therapeutic index, such as drug–herb interactions, matrix effects, and metabolic transformation. The review includes meta-analyses of clinical trials, emphasizing the influence of genetic variants on metabolism and interindividual variability in response patterns. A comparative examination of worldwide norms explores regulatory problems, highlighting the necessity for standardized quality assessment methodologies and jurisdictional differences. The safety concerns, dosage optimization, and regulatory frameworks controlling the therapeutic use of phytochemicals in cancer treatment are all rigorously discussed here. Despite the promising anticancer characteristics of plant-derived drugs, standardization, bioavailability, and potential toxicity pose significant obstacles to their clinical application. The impact of extraction techniques on drug purity, potency and the pharmacokinetic diversity across various patient populations are given special consideration. We also discuss the difficulties in determining bioequivalence and performing safety evaluations for botanical preparations that contain many components. In addition to offering evidence-based suggestions for maximizing the therapeutic use of plant-derived chemicals in oncology, our findings highlight the necessity of standardized procedures and harmonized regulatory frameworks in phytochemical research.