<p>Postoperative central nervous system infections (PCNSIs), including meningitis, cerebral abscesses, and implant-associated infections, represent critical complications following neurosurgical procedures. These infections pose significant risks to patient outcomes due to delayed diagnosis, escalating antimicrobial resistance, and limited therapeutic efficacy. Conventional diagnostic approaches, such as cerebrospinal fluid (CSF) analysis, microbial cultures, and neuroimaging, exhibit notable limitations in sensitivity, specificity, and rapidity. This review highlights transformative technologies reshaping PCNSI diagnostics, including molecular assays (e.g., quantitative PCR, digital droplet PCR), metagenomic next-generation sequencing (mNGS), CRISPR-based pathogen detection platforms, metabolomics, and advanced molecular imaging modalities. Furthermore, we address translational challenges in clinical adoption, including cost barriers, standardization gaps, and the need for interdisciplinary collaboration. Emerging artificial intelligence (AI)-driven strategies are proposed to optimize pathogen identification, predict antimicrobial resistance profiles, and tailor personalized therapeutic regimens.</p>