Redox dysregulation, ferroptosis evasion, and immune suppression are major barriers in cancer therapy. SH003, a multi-herbal formulation standardized under GMP conditions and evaluated in early-phase clinical studies (NCT03081819; KCT0004770), demonstrated a favorable safety profile supporting its translational potential. Preclinical studies reveal that SH003 disrupts mitochondrial homeostasis, triggers endoplasmic reticulum stress apoptosis, and sensitizes resistant tumors to ferroptosis via suppression of the SLC7A11–GPX4 axis and NRF2 destabilization. In parallel, SH003 remodels tumor immunity by attenuating STAT3-driven PD-L1 signaling, promoting macrophage repolarization, and enhancing cytotoxic lymphocyte activity. Exosome-associated microRNAs further suggest SH003’s role in redox–immune communication, although functional validation is pending. Collectively, SH003 represents a clinically tested phytomedicine that integrates ferroptosis induction with immune modulation, offering a biomarker-informed approach to precision oncology.