Background: Neurosyphilis is a severe manifestation of Treponema pallidum infection that may occur at any stage, particularly in cases of inadequate treatment or follow-up. Case Presentation: We report a case of a 55-year-old male with a prior history of treated syphilis who presented with progressive neuropsychiatric symptoms, including memory impairment, disorganized speech, and behavioral changes. Serial serological testing revealed a rising rapid plasma reagin (RPR) titer from 1:2 to 1:32 over time. Cerebrospinal fluid (CSF) analysis demonstrated elevated protein levels and a positive Treponema pallidum hemagglutination assay (TPHA 1:80), confirming the diagnosis of neurosyphilis despite a negative VDRL test in CSF. The patient was initially treated with ceftriaxone, followed by definitive therapy with intravenous benzylpenicillin for 14 days. Subsequent follow-up showed a gradual decline in RPR titers (1:32 to 1:1) along with clinical improvement. Conclusion This case underscores the importance of adequate post-treatment surveillance and highlights the need to consider neurosyphilis in patients presenting with neuropsychiatric symptoms and rising serological titers, even in the absence of positive CSF VDRL findings.