Nasal drug delivery is an effective therapeutic approach due to its rapid absorption, noninvasive administration, ability to bypass the blood–brain barrier (BBB), and avoidance of first-pass metabolism. This chapter focuses on in situ gelling hydrogels for nasal drug delivery. First, it reviews the anatomy and physiology of the nasal cavity, the mucosal layer, mucoadhesion mechanisms, and the mucociliary clearance (MCC) process. Then, it discusses various nasal formulations, including sprays, drops, powders, and gels, highlighting their specific advantages and limitations. Different in situ gelling systems, including temperature, ion, and pH-sensitive systems, as well as solid inserts, are also explained. Additionally, the preparation methods and drug release profiles of these systems, as well as multifunctional designs, including nanocomposite in situ gels, are discussed. Moreover, the characterization of these systems is organized into three categories: physicochemical properties, gel–mucus interactions, and advanced assessments. Microphysiological systems, an innovative technique, are introduced to simulate nasal environments and enhance understanding of drug delivery mechanisms. This approach aligns with the principles of New Approach Methodologies (NAMs), aiming to reduce reliance on animal testing while promoting ethical and regulatory advancements in drug development.