Tuberculous meningitis (TBM) is the most severe form of tuberculosis, causing high mortality and neurological disability. The dysregulated immune response contributes significantly to poor outcomes, and host-directed therapies (HDT) are needed to modulate this response. Recent advances in multiomics technologies, including proteomics, transcriptomics, and metabolomics, have improved our understanding of the host immune response in TBM. This review covers the entry of *Mycobacterium tuberculosis* (M. tuberculosis) into the central nervous system (CNS), microglial infection, blood-brain barrier (BBB) dysfunction, innate and adaptive immune responses, and metabolic and genetic factors. The review highlights the role of microglia in cytokine release, the impact of BBB dysfunction on leukocyte infiltration, and the involvement of inflammasomes, neutrophils, and cytokines in the inflammatory response. It also discusses the adaptive immune response, including T cells, B cells, and the tryptophan pathway, and the impact of host genetic factors and HIV-coinfection. The review concludes by discussing promising immunomodulatory therapies, research gaps, and future directions in TBM research.Tuberculous meningitis (TBM) is the most severe form of tuberculosis, causing high mortality and neurological disability. The dysregulated immune response contributes significantly to poor outcomes, and host-directed therapies (HDT) are needed to modulate this response. Recent advances in multiomics technologies, including proteomics, transcriptomics, and metabolomics, have improved our understanding of the host immune response in TBM. This review covers the entry of *Mycobacterium tuberculosis* (M. tuberculosis) into the central nervous system (CNS), microglial infection, blood-brain barrier (BBB) dysfunction, innate and adaptive immune responses, and metabolic and genetic factors. The review highlights the role of microglia in cytokine release, the impact of BBB dysfunction on leukocyte infiltration, and the involvement of inflammasomes, neutrophils, and cytokines in the inflammatory response. It also discusses the adaptive immune response, including T cells, B cells, and the tryptophan pathway, and the impact of host genetic factors and HIV-coinfection. The review concludes by discussing promising immunomodulatory therapies, research gaps, and future directions in TBM research.