Endoscopic full-thickness resection (EFTR) is a minimally invasive technique primarily indicated for the removal of gastrointestinal lesions that are unsuitable for traditional endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Indications for EFTR include gastrointestinal stromal tumors (GISTs), subepithelial tumors (SETs) originating from the muscularis propria, and certain high-risk adenomas or early-stage cancers that exhibit submucosal invasion or are located in difficult-to-reach areas. EFTR has two main methods: exposed and nonexposed. Within the exposed technique, EFTR can be tunneled or non-tunneled. In tunneled EFTR, a mucosal incision and tunnel are created to access and resect submucosal lesions, requiring only mucosal defect closure. Non-tunneled EFTR involves dissecting around a lesion with extensive muscularis propria involvement, necessitating full-thickness closure. Nonexposed EFTR involves invaginating the lesion into the lumen for serosa-to-serosa apposition before resection, often using the full-thickness resection device (FTRD), suitable for lesions in the colon, stomach, and duodenum. EFTR combines the benefits of endoscopic and surgical approaches, offering a less invasive option with shorter recovery times and fewer complications. Its efficacy and safety make it a valuable tool in the management of complex gastrointestinal lesions, expanding the therapeutic options available to patients.