Abstract The discovery of diverse molecular mechanisms of regulated cell death has opened new avenues for cancer therapy. Ferroptosis, a unique form of cell death driven by iron-catalyzed peroxidation of membrane phospholipids, holds particular promise for targeting resistant cancer types. This review critically examines current literature on ferroptosis, focusing on its defining features and therapeutic potential. We discuss how molecular profiling of tumors and liquid biopsies can generate extensive multi-omics datasets, which can be leveraged through machine learning-based analytical approaches for patient stratification. Addressing these challenges is essential for advancing the clinical integration of ferroptosis-driven treatments in cancer care.