Cisneros' wealth comes from his holdings in media, entertainment, telecommunications and consumer products companies. The Cisneros Group of Companies is one of the largest privately-held media and entertainment companies in the world. Cisneros is also the largest shareholder in Univision, the United States' leading Spanish-language television network and owns Venevision International, which produces and distributes media and entertainment products throughout the world.

Long an advocate of free enterprise, Cisneros has for many years been expanding his operations out of Venezuela and into overseas markets, including the U.S. and more recently China. He owns Venevision, Venezuela's leading television network. Following the recent democratic consolidation of power in Venezuela under President Hugo Chávez, Cisneros has toned down criticism of the Chávez regime by his network and focused on the Cisneros business overseas. One of his major accomplishments has been a major role in the international development of the telenovela – emotion-packed melodramas based on the harsh realities of life in Latin America that are now broadcast to about 2 billion people around the world. In part to honor his international success he was named MIPCOM "Personality of the Year" in 2005, a prestigious media industry award.

The Cisneros Foundation (Fundacion Cisneros) runs a wide range of educational and cultural programs aimed at improving the lives of Latin Americans.

Cisneros is also pinpointed as a key player in the April 2002 coup attempt against Hugo Chávez by the American-Venezuelan human rights attorney Eva Gollinger in her book The Chavez Code and also in the Irish television documentary The Revolution Will Not Be Televised. In 2004, a group of Colombians were found on his ranch near Caracas that were allegedly going to be utilized as part of a coup attempt against the Venezuelan government.