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Background: Streptococcus pneumoniae, a major contributor to global morbidity and mortality, disproportionately affects children, the elderly, and immunocompromised individuals. Despite vaccination efforts, the challenge of serotype replacement highlights the ongoing struggle against invasive pneumococcal diseases (IPD) in Morocco, emphasizing the need for updated public health strategies and vaccine efficacy assessments. Methods: This study was conducted at the Ibn Rochd University Hospital Center and the Mohammed VI University Hospital Center from 2019 to 2022, focusing on hospitalized children. It involved the analysis of 74 strains of IPD, assessing the distribution of pneumococcal serotypes and their antibiotic sensitivity in the post-vaccination era. Results: The prevalence of meningitis or meningo-encephalitis was found to be 66% among the study subjects, with the most frequent serotypes being 3, 19A, 6B, 14, and 11. These serotypes varied significantly by age and location. Coverage rates for the pneumococcal conjugate vaccines, PCV-10 and PCV-13, were 20.27% and 56.75%, respectively. Notably, 43% of the strains were non-vaccine serotypes, with serotypes 3 and 19 accounting for 36% of the infections in children, indicating a lack of vaccine efficacy against these types. Additionally, 31.3% of the strains were Penicillin non-susceptible Streptococcus pneumoniae (PNSP), with 81.25% associated with nonvaccine serotypes. Conclusions: This study highlights the persistence of IPD in Moroccan children, revealing significant challenges despite vaccination efforts. With the reintroduction of PCV-13, concerns about the efficacy against non-vaccine serotypes, particularly 3 and 19A, remain. Continuous surveillance and adaptable vaccination strategies are essential to combat these serotype replacements and ensure the effectiveness of future preventive measures. [ABSTRACT FROM AUTHOR]