Our review delves into the realm of peroral endoscopic myotomies (POEMs) in the upper gastrointestinal tract (UGT). In recent years, POEMs have brought about a revolution in the treatment of UGT motility disorders. Esophageal POEM, the first to be introduced, has now been validated as the primary treatment for achalasia. Subsequently developed, G-POEM displays promising results in addressing refractory gastroparesis. Over time, multiple endoscopic myotomy techniques have emerged for the treatment of Zenker’s diverticulum, including Z-POEM, POES, and hybrid approaches. Despite the well-established efficacy outcomes, new challenges arise in the realm of POEMs in the UGT. For esophageal POEM, the future scenario lies in customizing the myotomy extent to the minimum necessary, while for G-POEM, it involves identifying patients who can optimally benefit from the treatment. For ZD, it is crucial to validate an algorithm that considers various myotomy options according to the diverticulum’s size and in relation to individual patients. These challenges align with the concept of precision endoscopy, personalizing the technique for each subject. Within our text, we comprehensively examine each myotomy technique, analyzing indications, outcomes, and adverse events. Additionally, we explore the emerging challenges posed by myotomies within the context of the evolving field of precision endoscopy.