Despite a high success rate of over 80%, root canal treatments often result in tooth loss, primarily due to persistent intra-radicular biofilms. These biofilms are difficult to eliminate because of the complex anatomy of root canal systems. Recent innovations in disinfection technologies, including laser-assisted irrigation (LAI) and multi-sonic systems like GentleWave, have shown promise in improving microbial elimination without excessive structural compromise. Er:YAG lasers are preferred over Er,Cr:YSGG lasers for their superior absorption in water and reduced risk of thermal damage. LAI, particularly with photon-induced photoacoustic streaming (PIPS), has demonstrated greater efficacy than traditional irrigation and passive ultrasonic irrigation (PUI), although its success is still highly dependent on irrigant properties. The GentleWave system enhances debridement through hydrodynamic cavitation and acoustic streaming, proving effective even in minimally prepared canals. Similarly, OdneClean shows potential as a cavitation-based device but requires further validation in clinical conditions. However, none of these methods restore the mechanical integrity of treated teeth. To address this limitation, a novel chitosan nanotechnology has been developed to reinforce root dentin and promote healing through immunomodulation. Photoactivated chitosan nanoparticles improve dentin biomechanical properties, stabilize the matrix, and modulate immune responses to support tissue repair and reduce inflammation. Although further clinical evidence is needed, the integration of advanced disinfection strategies and bioactive nanotechnology offers a promising future for improving outcomes in endodontic therapy, particularly in teeth with complex anatomy or previously guarded prognoses. These innovations represent a significant shift toward biologically driven and structurally supportive endodontic care.