Objective: This study aimed to describe the epidemiology, clinical characteristics, management, and treatment outcomes of patients diagnosed with central nervous system (CNS) infections at a tertiary care hospital in Egypt. Methods: A retrospective analysis was conducted on 104 patients admitted with suspected CNS infections between July 2021 and October 2023. Data extracted from hospital records included patient demographics, clinical features, laboratory and neuroimaging results, treatment regimens, and final outcomes. Results: The median patient age was 50 years, with a male predominance (71.2%). The most common diagnoses were encephalitis (45.2%) and meningitis (41.3%). A causative pathogen was identified in only 42.3% of cases, with Streptococcus pneumoniae being the most frequent (13.5%). No etiology was found in 57.7% of cases. Diabetes was the most frequent comorbidity (27.9%). The universal clinical feature was disturbed consciousness, followed by fever and headache. The most used empirical treatment was a combination of ceftriaxone, vancomycin, and acyclovir (57.6%). The overall cure rate was 80.7%, and the mortality rate was 5.7%. All cases of cryptococcal meningitis and 10% of cerebral malaria cases were fatal. Conclusion: In this cohort, CNS infections primarily affected older adults, with a high rate of unknown etiology. The use of empirical broad-spectrum therapy was associated with a favorable overall outcome. However, the findings highlight an urgent need for enhanced diagnostic methods to identify pathogens, especially in fatal fungal and parasitic infections, to guide targeted treatment and potentially improve survival.