Background: Post-herpetic neuralgia (PHN) is a common and disabling complication of herpes zoster in older adults. Pregabalin and nortriptyline are frequently used in combination for neuropathic pain and are generally well tolerated; however, their combined neuroactive effects may rarely result in adverse neurological outcomes. Case Report: A 65-year-old male with thoracic PHN developed acute unilateral lower limb neuropathy progressing to monoplegia within five days of initiating a fixed-dose combination of pregabalin (75 mg) and nortriptyline (10 mg). Neuroimaging and laboratory investigations excluded metabolic, infectious, and structural causes. Discontinuation of the offending drugs and initiation of neuroregenerative therapy resulted in complete neurological recovery within two weeks. The adverse event was classified as a probable drug reaction (Naranjo score = 6). Conclusion: This case highlights a rare but reversible neurological adverse effect of combined pregabalin–nortriptyline therapy, emphasizing the need for cautious use, early recognition, and vigilant monitoring in elderly patients.