Meningitis in individuals living with acquired immunodeficiency syndrome (AIDS) is most frequently infectious in origin and usually due to opportunistic infections. The most common pathogens are Cryptococcus neoformans and Mycobacterium tuberculosis. Treponema pallidum causes neurosyphilis and can complicate HIV infections at any time after the initial infection. Simultaneous infections of the central nervous system caused by these pathogens are very uncommon even in the setting of severe immunosuppression. We report the case of a newly diagnosed HIV/AIDS young man who was found to have neurosyphilis with Cryptococcus meningitis. After a few weeks of treatment and initiation of antiretroviral therapy, he was also diagnosed with tuberculous meningitis, which was probably unmasked by the development of immune reconstitution inflammatory syndrome (IRIS). To the best of our knowledge, this is the only case of reported neurosyphilis and meningitis caused concomitantly by Cryptococcus and Mycobacterium tuberculosis.