Endoscopy is now widely used as a therapeutic platform for various diseases in the upper GI tract. A working space of the endoscopic treatments is no longer confined to the internal lumen but extends to the submucosal space or external cavity. Submucosal endoscopy, that uses a submucosal layer as a novel working space or safety entrance to the external cavity for endoscopic interventions, is now recognized as a therapeutic option for esophageal achalasia, Zenker’s diverticulum, removal of subepithelial or mediastinal tumor, gastric paresis, etc. In the last few decades, a series of suturing devices have been developed to enable secure and durable closure of a full-thickness wound. This technique has been a long-lasting dream for endoscopists to accomplish urgent perforation closure, full-thickness resection, natural orifice translumenal surgery, and endoluminal bariatric therapy. Besides, other novel endoscopic treatments such as endoscopic duodenal mucosal resurfacing, endoscopic vacuum therapy, etc. are performed as an investigational treatment. In this symposium, we would share the information of new endoscopic technologies and techniques, and seek the future direction of therapeutic upper GI endoscopy through discussion.