The purpose of this study was to systematically review the impact of nanofillers on the physicomechanical properties of resin-based pit and fissure sealants (RBS). This review included in vitro studies with full-length English-language articles reporting on the physicomechanical properties of nanofilled RBS until February 2023. PubMed, Web of Sciences, Scopus, and LILACS databases were accessed for literature searches. The review was formulated based on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and used the Consolidated Standards of Reporting Trials (CONSORT) guidelines and risk of bias Cochrane tool for quality assessment. The search resulted in 539 papers, of which 22 were eligible to be included in the review. Inorganic, polymeric, core-shell, and composite nanomaterials were used to reinforce the studied RBS. The inherent nature of the nanomaterial used, its morphology, concentration, and volume used were the primary parameters that determined the nanomaterial's success as a filler in RBS. These parameters also influenced their interaction with the resin matrix, which influenced the final physicomechanical properties of RBS. The use of nanofillers that were non-agglomerated and well dispersed in the resin matrix enhanced the physicomechanical properties of RBS.