The concept of third space endoscopy is based on the principle that the deeper layers of the gastrointestinal tract can be accessed by tunneling in the submucosal space and maintaining the integrity of the overlying mucosa. The mucosal flap safety valve enabled endoscopists to use submucosal space securely. The era of third space endoscopy started with peroral endoscopic myotomy for treatment of achalasia and has expanded to treat various other gastrointestinal disorders, such as mucosal lesions, submucosal tumors, extraluminal tumors, and refractory gastroparesis, Zenker diverticulum, and restoration of the completely obstructed esophageal lumen. Third space endoscopy rapidly emerged as a minimally invasive alternative to conventional surgery. Many studies discovered that this technique is safe and effective with excellent outcomes. Our review focused on the indications, techniques, clinical management, and adverse events of submucosal tunneling techniques for tumor resection.