He is one of the key television figures in favor of the Philippine drug war undertaken by the administration of President Rodrigo Duterte.

After the ousting of Marcos in 1986, de Castro joined ABS-CBN, as the segment host for "At Your Service" of Good Morning!

During his term as Vice President of the Philippines from 2004 to 2010, On July 2, 2005, to June 28, 2010, he co-anchored the program Para Sa'yo, Bayan, which aired weekly on DZMM.

[10] On November 8, 2010, he returned as an anchor of TV Patrol, replacing Julius Babao who left the newscast as the latter would move to Bandila alongside Karen Davila.

[15] De Castro, along with Persida Acosta, amplified the possibility of Dengvaxia vaccination, which began during former President Aquino's term, as the cause of death of children in the Philippines.

Various organizations have blamed de Castro and Acosta for their misinformation which led to the deaths of numerous Filipino youths due to a "vaccination scare campaign".

He also became the host of the new public affairs program KBYN: Kaagapay ng Bayan on Kapamilya Channel, TeleRadyo and A2Z; it aired until January 1, 2023.

[17] On January 9, 2023, he returned to TV Patrol for his third stint, joining Bernadette Sembrano, Henry Omaga-Diaz and Karen Davila, coinciding with the celebration of the Feast of the Black Nazarene.

As HUDCC Chair, Vice President de Castro also serves as ex officio chairman of the Home Development Mutual Fund (HDMF or Pag-IBIG Fund), the Housing and Land Use Regulatory Board (HLURB), the National Housing Authority (Philippines) (NHA), the National Home Mortgage Finance Corporation (NHMFC) and the Social Housing Finance Corporation (SHFC) as well as ex officio vice chairman of the Home Guaranty Corporation (HGC).

He has also been designated as concurrent presidential adviser on overseas Filipino workers, as alternate chairman of the National Anti-Poverty Commission, head of the Task Force Against Illegal Recruitment, price monitoring czar and cabinet officer for Regional Development Palawan.

In an interview conducted by Karen Davila, he announced that he would retire from politics at the end of his vice presidential term and intended to commit himself full time to broadcast journalism.