Pulpectomy has always been a treatment choice when irreversible damage to the pulpal and periapical tissues occurs, but in a pediatric patient, expecting cooperation and adequate chair side time is a huge task as they fear the dentists and the instruments. Hence, it was required that there come an advanced treatment protocol that helps overcome the drawbacks of the existing treatment modality. A new therapeutic strategy called lesion sterilization and tissue repair (LSTR) is revolutionizing how dental lesions are treated today. Through a non-invasive antimicrobial treatment, this cutting-edge method seeks to halt the spread of carious lesions while encouraging tissue repair and regeneration. In LSTR, the infected tooth tissues are treated directly with a special antimicrobial combination of antibiotics, reducing agents, and disinfectants. Through the elimination of the microorganisms that cause dental decay and the creation of an environment that is favorable for natural tissue healing, this intervention targets the microbial etiology. This article mainly focuses on using antibiotics as a treatment modality in a tooth affected by caries and where the pulp and periradicular tissues are irreversibly inflamed. Pulpectomy has always been the most practiced technique, but in children, due to the lack of cooperation during the treatment and harm to the underlying developing tooth bud, a less invasive protocol had to be used, which is LSTR. This review delves into the basic ideas, techniques, and clinical applications of lesion sterilization and tissue restoration to look at its various aspects. This review clarifies the effectiveness and safety of LSTR in controlling diverse dental diseases, ranging from early-stage caries to deep dentin infections, by critically assessing previous study findings. It also emphasizes LSTR's ability to preserve vital tooth pulp, obviating the need for invasive and frequently uncomfortable endodontic operations. The review advocates for integrating LSTR into contemporary dental practices, showcasing its potential to transform the landscape of oral healthcare. By providing a comprehensive overview of this innovative technique, this review encourages further research and clinical implementation, heralding a new era in dentistry focused on preservation, regeneration, and enhanced patient well-being.