Mowat-Wilson Syndrome (MWS) is an autosomal dominant genetic syndrome caused by mutations in the ZEB2 gene. It is characterized by distinctive facial appearance, intellectual disability (ID), epilepsy, Hirschsprung disease (HSCR), and other congenital anomalies. The psychiatric symptoms, associated with MWS have rarely been reported. The following report highlights a case of schizoaffective disorder in a 24-year-old male with MWS and the challenges he encountered over his treatment course. After considering numerous diagnoses including bipolar disorder and psychosis secondary to a general medical condition, the patient was diagnosed with schizoaffective disorder. Various trials consisting of atypical antipsychotics and mood stabilizers were unsuccessful in managing his symptoms. Eventually, the patient stabilized on a medication regimen consisting of clozapine 300 mg once daily, topiramate 75 mg twice per day, and lithium 1800 mg once daily. This case report documents co-occurrence of MWS and Schizoaffective disorder.