Introduction: The combination of trigeminal neuralgia (TN), glossopharyngeal neuralgia (GPN), and hemifacial spasm (HFS), referred to as combined hyperactive dysfunction syndrome (HDS), is a rare disorder characterized by paroxysmal severe pain and tic convulsions in the innervation region. Interestingly, there is no evidence of the coexistence of TN and GPN with nervus intermedius neuralgia (NIN) in the literature. Method: A 50-year-old man who was surgically treated for two months prior to presentation with paroxysmal pain in the left cheek, tooth root, and tongue, posterior pharyngeal wall, deep ear, and earlobe. Case Presentation: He began experiencing posterior alveolar discomfort a year ago and had his bottom posterior teeth pulled two months ago. It is worth noting that he typically takes ibuprofen orally (0.6 similar to 2.4 g per day) to alleviate discomfort associated with paroxysmal condition. Results: Our diagnosis was verified by preoperative magnetic resonance tomographic angiography (MRTA) and intraoperative results. We conducted neurological surgery on these constricted nerves by performing microvascular decompression (MVD). Teflon materials were employed to isolate the artery and nerve enough. TN, GPN, and MN all ceased to exist immediately after our operation. Discussion: Our case is the first coexisting TN, GPN, and NIN patient who underwent MVD surgery after immediate termination of drug treatment. Ibuprofen therapy on a chronic basis may reduce neuropathic pain but has no neuroprotective impact. Nonsteroidal anti-inflammatory medication usage in the clinic incorrectly may have extra detrimental consequences and disrupt the peripheral neuro-environment of cranial nerves. MVD through the suboccipital retrosigmoid route is an excellent treatment option for such coexisting cranial neuralgia.