A 3-year-old neutered female domestic shorthair cat was presented with a severely pruritic dermatitis. After exclusion of flea allergy dermatitis, ectoparasite infestation, retroviral infection, neoplasia, and cutaneous adverse food reaction, a diagnosis of nonflea, nonfood hypersensitivity dermatitis (NFNFHD) was made. The resolution of complicating bacterial infection and yeast overgrowth did not improve the animal's condition. Numerous antipruritic treatment modalities used during the investigation proved unsuccessful, including anti-inflammatory and immunosuppressive prednisolone doses, oclacitinib, antihistamines, ciclosporin A, and supplementation with essential fatty acids. Allergen-specific serology test results were negative. Treatment with oral dexamethasone allowed a complete resolution of clinical signs. The cat has been successfully maintained in remission for over 12 months. To the author's knowledge, this is the first case report of a cat with multi-drug-resistant NFNFHD treated successfully with dexamethasone.