Background: Nanotechnology has emerged as a promising field for the diagnosis, monitoring, and treatment of respiratory tract infections (RTIs). By leveraging the unique properties of nanoscale delivery systems, nanotechnology can significantly enhance the selectivity and efficacy of antimicrobials, thereby reducing off-target effects. Objective: This review explores the development and application of targeted nanosystems in combating viral, bacterial, and fungal RTIs. Nanotechnology-based systems, including biological and non-biological nanoparticles, offer innovative solutions for overcoming antimicrobial resistance, improving drug bioavailability, and minimizing systemic side effects. RTIs are a leading cause of morbidity and mortality globally, particularly affecting vulnerable populations such as children, the elderly, and immunocompromised individuals. Traditional drug delivery methods face numerous challenges, such as rapid clearance, poor tissue penetration, and drug degradation. Nanoparticle-based delivery systems address these issues by enhancing tissue penetration, providing sustained drug release, and enabling targeted delivery to infection sites. These systems include liposomal delivery, polymeric nanoparticles, dendrimers, and metal-based nanoparticles, each offering unique advantages in treating RTIs. Nanotechnology also plays a crucial role in vaccine development by offering new strategies to enhance immune responses and improve antigen delivery. Furthermore, the review discusses the clinical translation and regulatory considerations for nanotechnology-based drug delivery, emphasizing the need for rigorous testing and quality control to ensure safety and efficacy. Conclusion: Nanotechnology offers promising advancements in the treatment, and prevention of RTIs by enhancing drug delivery and efficacy. By addressing challenges such as antimicrobial resistance and poor tissue penetration, nanotechnology-based systems have the potential to significantly improve patient outcomes.