This study aimed to elucidate the bacterial and viral etiologies of meningitis, focusing on their mechanisms of central nervous system (CNS) invasion and associated host immune responses. We conducted a comprehensive analysis of 250 meningitis cases from multiple healthcare centers, employing microbiological cultures, polymerase chain reaction (PCR), and cytokine assays to identify pathogens and characterize their invasion strategies and immune responses. Our findings revealed that bacterial meningitis predominates, especially in younger age groups, while viral meningitis is more broadly distributed across ages. Mechanistically, bacterial pathogens frequently utilize hematogenous spread, whereas viral pathogens often exhibit both hematogenous and direct neural invasion. Immune response analysis showed significantly higher levels of inflammatory markers (IL-6, TNF-alpha, IFN-gamma) in bacterial cases compared to viral ones. These results suggest that bacterial meningitis triggers a more intense immune response, correlating with the observed severity. The study highlights the need for targeted treatments based on pathogen type and invasion mechanism to improve clinical outcomes