Oral bacteria have been associated with several systemic diseases. Moreover, the abundance of bacteria associated with caries has been found to be higher in patients with congenital heart disease (CHD) than in healthy control groups (HCGs). Therefore, this study aimed to evaluate the dental microbiota in children with CHD compared to a HCG. The aim was to describe and compare the carious microbiome regarding the composition, diversity, and taxonomic patterns in these two groups. Twenty children with CHD and a HCG aged between two and six years participated. All of them were affected by early childhood caries. Microbiome profiling indicated that Fusobacterium, Prevotella, Capnocytophaga, and Oribacterium were more abundant in the CHD group, whereas Lactobacillus and Rothia were predominant in the HCG. Furthermore, microbiome analysis revealed three distinct clusters for the CHD and HCG samples. In the first cluster, we found mainly the genera Lactobacillus and Coriobacteriaceae. The second cluster showed a higher relative abundance of the genus Actinomyces and a more diverse composition consisting of more genera with a smaller relative lot. The third cluster was characterized by two genera, Streptococcus and Veillonella. These data can help us to understand the oral microbial community structures involved in caries and endodontic infections of pre-school children in relation to the general health of these high-risk patients.