Inborn errors of immunity (IEIs) are genetic disorders that impair immune defense and regulation, increasing susceptibility to infections, including those in the oral cavity. The oral microbiota plays a vital role in maintaining oral health, and in pediatric patients with IEIs, disruptions in this balance can lead to dental caries and other oral diseases. This chapter provides a comprehensive analysis of the relationship between immune deficiencies and oral microbiota dysbiosis, focusing on dental caries in children with IEIs. Omics technologies, particularly metagenomics, have enhanced understanding of the microbial diversity and metabolic activities within the oral microbiota of the patients. Key findings reveal that compromised immune responses in children with IEIs disrupt the balance of oral bacteria, making them more prone to dental caries. The chapter highlights the importance of an interdisciplinary approach, integrating microbiology, immunology, dentistry, and bioinformatics, to uncover the complex interactions between the oral microbiome and the immune system. The insights gained from this research will contribute to the development of personalized therapeutic strategies, improving the dental and overall health of pediatric patients with IEIs.