Targeted drug delivery systems are designed to administer pharmaceutical agents precisely to diseased areas, enhancing treatment efficacy while minimizing side effects. Various carriers—such as antibodies, transdermal patches, biodegradable polymers, nanoparticles, liposomes, niosomes, and microspheres—are employed in these systems. Among them, niosomes represent a promising and innovative class of vesicular systems. Niosomes, or non-ionic surfactant vesicles, have attracted significant attention in the pharmaceutical industry due to their versatile ability to encapsulate both hydrophilic and hydrophobic drugs. Recent research highlights their potential to improve drug bioavailability, making them an effective strategy for delivering diverse therapeutic agents, including gene materials, protein therapeutics, and chemical pharmaceuticals, with minimal toxicity and effective targeting. Niosomes possess non-immunogenic properties and can be engineered for controlled drug release, enabling a steady and prolonged delivery that reduces side effects and enhances therapeutic outcomes. Compared to liposomes, niosomes exhibit superior stability during preparation and storage, as liposomes are generally more prone to enzymatic degradation and leakage of encapsulated compounds. Optimizing niosomal components or surface characteristics can achieve desired pharmacokinetic profiles. Furthermore, niosomal systems are relatively easy to develop and scale up while maintaining cost-effective manufacturing. This review article elucidates the fundamentals of niosomes as non-ionic surfactant vesicles, covering their structure, components, and various formulation methods. Additionally, it explores the diverse applications of niosomes in analgesic drug delivery.