Building on the success and momentum of the first edition of the special issue of “Personalized Medicine for Otolaryngology”, its reprint was published as an MDPI book edited by Dr. Mehdi Abouzari. The second edition of this special issue will be co-edited by Drs. Mehdi Abouzari and Sepehr Oliaei. The second edition aims to capture the latest breakthroughs and emerging challenges in personalized ENT care. This special issue seeks to provide a comprehensive, forward-looking overview of how personalized medicine is improving patient survival, functional outcomes, and quality of life across the entire spectrum of otolaryngology—from bench to bedside and beyond.