Over the years, our growing experience with endoscopic submucosal dissection along with technological advances has solidified our comfort and knowledge on working in the submucosa, also referred to as the "third space." Per-oral endoscopic myotomy (POEM) was the first prototype third-space endoscopy (TSE) procedure, demonstrating the feasibility and clinical utility of endoscopic esophagogastric myotomy via submucosal tunneling. The launch of POEM accelerated the evolution of TSE from a vanguard concept to an expanding field with a wide range of clinical applications. In this review, we discuss the status and future directions of multiple TSE interventions.