This is a case of a four-month-old female infant who presented with clinical manifestations of congenital rubella syndrome (CRS) -bilateral cataracts, poorly-dilating pupils, microcorneas, salt and pepper retinopathies seen after cataract extractions, bilateral sensorineural hearing loss, patent ductus arteriosus, microcephaly, history of blueberry spots and low birth weight, and positive serum IgM and IgG tests for rubella. The patient's mother also had prenatal rubella infection. However, the patient also presented with additional set of clinical findings not seen in recent patients with CRS and not commonly reported in literature: visual acuities of poor to no dazzle, bilateral choroidal thickening on ocular ultrasound that spontaneously resolved, optic nerve inflammation that became atrophic, vessel tortuosities seen after cataract extractions, bilateral subependymal cysts with lenticulostriate vasculopathy in basal ganglia, basal ganglia hyperintensity suggestive of calcification, and jaundice. These findings plus the overlapping clinical manifestations with CRS and the positive IgM and IgG for cytomegalovirus (CMV) made us consider a congenital CMV co-infection.CRS already causes significant childhood morbidity. Getting co-infected with CMV in utero worsens morbidity and makes management more difficult. This case presented a congenital co-infection of rubella and CMV and discussed the added challenges in their diagnosis and management.