The COVID-19 pandemic, driven by SARS-CoV-2, has led to intensive vaccination campaigns worldwide. Despite widespread vaccination, the potential for vaccine escape variants necessitates ongoing research into the virus’s intra-host evolutionary dynamics. In this study we investigated the effects of vaccination on SARS-CoV-2 intra-host evolution during the Delta and Omicron waves in São Paulo, Brazil, analyzing 700 SARS-CoV-2 positive samples collected through the LabMovel initiative, from August 2021 to March 2022. Samples were categorized based on vaccination status (Unvaccinated, Spike protein-based vaccines, and Whole inactivated virus vaccine), enabling comparison of intra-host viral diversity across vaccinated and unvaccinated individuals for both Delta and Omicron VOCs. We evaluated intra-host genetic diversity by measuring intra-host single nucleotide variants (iSNVs), Faith's Phylogenetic Diversity (PD), and haplotype diversity using Normalized Shannon Entropy. For Delta, vaccinated groups exhibited higher haplotype diversity, yet no statistically significant difference was observed in the total number of iSNVs between vaccinated and unvaccinated individuals. Selective pressures in the Delta VOC showed neutral selection in vaccinated individuals, contrasting with purifying selection in unvaccinated individuals, though effect sizes were minimal. For Omicron, a bimodal distribution in Faith's PD across all groups suggests genetic drift events, aligning with Omicron’s rapid spread and high transmissibility. Observed intra-host diversity patterns were variant-specific, with Spike-based vaccines associated with a lower number of haplotypes in Omicron cases. These findings suggest that vaccination modulates SARS-CoV-2’s intra-host evolution, likely contributing to its mutational landscape in a variant-dependent manner. The results highlight variant-specific responses to vaccination, emphasizing the complex role of selective pressures in SARS-CoV-2 intra-host evolution. Our findings support ongoing genomic surveillance to understand vaccination's evolutionary impact on intra-host viral dynamics, particularly as new variants emerge.