In 2003, he played for the Cleveland Indians and in 2004, he signed with the Chicago White Sox organization, though he saw no time in the majors that year.

After that, Santiago was a member of the Puerto Rico national team in the 2006 World Baseball Classic and joined the Olmecas de Tabasco for the rest of the summer.

In addition to playing for the New Orleans Zephyrs in the Mets farm system In 2008, Santiago pitched for the Gigantes de Carolina Puerto Rico representing team in the Caribbean Series.

In between, Santiago played winter ball with the Cardenales de Lara and Leones del Caracas clubs of the Venezuelan Professional Baseball League.

Santiago runs a college placement program in Puerto Rico called Optimus Prospects Baseball Academy.