The COVID-19 pandemic, caused by SARS-CoV-2, highlights the need to understand the virus’s genomic diversity and evolution. This study analyzes SARS-CoV-2 data from Mauritania and Morocco using molecular diagnostics and bioinformatics tools. In Mauritania, 58 nasopharyngeal samples were analyzed through RNA extraction, RT-PCR detection, and complete genome sequencing using the Illumina COVIDSeq protocol. Moroccan sequences were retrieved from the GISAID database for comparative analysis. Key bioinformatics tools, including MEGA X and Genome Detective, were used to identify variants, mutations, and evolutionary relationships. The results reveal the prevalence of Omicron subvariants (BA.2 and BA.5) in both regions, with notable differences such as the persistence of Delta in Mauritania and the dominance of Omicron in Morocco. These findings emphasize the importance of genomic surveillance and molecular tools to guide public health strategies.