Irreversible electroporation (IRE) is a non-thermal ablation modality that employs high-intensity, short-pulsed electric fields to induce irreversible cell membrane damage. It has garnered increasing attention for the treatment of tumors located in anatomically complex locations. For tumors adjacent to critical structures such as major blood vessels, bile ducts, and nerves, conventional surgery often entails substantial trauma and elevated perioperative risks, whereas thermal ablation is constrained by the risk of collateral thermal injury and the heat sink effect, which may compromise both therapeutic efficacy and patient safety. In contrast, IRE slectively eliminates local lesions through permanent membrane permeabilization while preserving the integrity of vascular and ductal structures, thereby offering distinct advantages in challenging regions including the pancreatic head, hepatic hilum, renal hilum, and prostate. Moreover, emerging evidence suggests that IRE may potentiate anti-tumor immune responses by inducing immunogenic cell death and remodeling the tumor microenvironment. This review summarizes the mechanisms of action, technical advantages, clinical efficacy and safety of IRE in tumors arising from various complex anatomical sites, and also discusses current challenges and future directions for this promising technique.