Endodontic-periodontal disorders are influenced by the complex microbiota of periodontal pockets and the microorganisms in root canals (RCs). Utilizing cutting-edge sequence information, this research conducted a systematic analysis to evaluate the microbial makeup of infected RCs and PPs to evaluate the microbiota and confirm the potential for contamination between these two sites. This study compiles, combines, and analyzes information based on a thorough literature evaluation. Following a predetermined protocol, sixteen research articles were chosen from seven databases between 2014 and 2024. The V3-V4 hyper-variable portion of the 16S rRNA gene was the primary concern of examining the microbiomes of these coupled illnesses. There were more periodontal pocket species than RC species, with obligate anaerobes and gram-negative bacteria predominating. The genera Enterococcus, Parvimonas, and Stomatobaculum were predominant in the RCs; however, the PPs showed that Enterococcus, Parvimonas, Stomatobaculum, Peptostreptococcus, and Mogibacterium were predominant. Regarding sharing OTUs for species and genera, the RC and PP microbiomes differed correspondingly. The molecular marker screening found numerous markers for resistance to beta-lactam and carbapenem antibiotics (broad spectrum). The study identified markers for systemic disorders affecting the heart muscle and rheumatology, while additional diseases were another noteworthy finding. In 2022, we have seen growing trends in the articles. Most articles have examined the anatomical aspects in the subject. In conclusion, the RC microbiota could have been more varied and sophisticated than the PP. There were interconnections throughout the microbial communities. The same genus may show communication between the periodontal and endodontic microbiomes.