Millions of people worldwide suffer from cancer, facing challenges such as treatments affecting healthy cells, suboptimal responses, adverse effects, recurrence risk, drug resistance, and nonspecific targeting. Chemoresistance leads to fatalities, but phytoactives show promise in cancer management despite limitations such as high metabolism, poor absorption, and high dosage requirements. Challenges in the large-scale isolation of phytoactive compounds, solubility, bioavailability, and targeting limit their development. Recent developments, including carbohydrate, lipid, and protein-based nanoparticles, have enhanced cancer treatment by improving the bioavailability and targeted delivery of phytoactives such as polyphenols, alkaloids, sulfur-containing compounds, flavonoids, and terpenes. Despite advancements, clinical application faces hurdles such as poor bioavailability and inconsistent immune responses. This article discusses the promise of phytoactive-loaded nanoformulations in cancer management, highlighting targeted drug delivery, unmet needs, and challenges. Further research is needed to overcome these challenges and fully understand the potential of phytoactives in cancer management.