Congenital heart diseases, hemolytic anemia, collagen vascular diseases, and neurometabolic disorders are known to be associated with the development of arterial ischemic stroke (AIS) in children. However, not all the children with the aforementioned conditions develop AIS. Hence, the possibility of interplay of various predisposing factors in children with inherent underlying medical conditions seems likely. Trauma, infections, and thrombophilic risk factors are well known to predispose to the development of AIS in children. Congenital hypoplasia of internal carotid artery (HICA) is a rare disorder in which patient may remain asymptomatic or may present with symptoms due to cerebrovascular insufficiency or compression by collateral vessels. We report a 7-year-old boy who presented with AIS and had a history of two transient ischemic attacks in the past 2 years. He was diagnosed to have congenital HICA. However, further evaluation revealed the presence of protein S deficiency as well. This case reemphasizes the need for investigation into multifactorial causation of pediatric AIS in every case.