María Jesús Montero began her institutional career in the Regional Government of Andalusia, where she served as Regional Vice Minister of Health from 2002 to 2004, Regional Minister of Health from 2004 to 2012, and Regional Minister of Health and Social Welfare until 2015. During this period, she was also a Member of the Parliament of Andalusia (2008–2018).  

In addition, she served as Spokesperson of the Government of Spain from January 2020 to July 2021. In November 2023, she was appointed Fourth Deputy Prime Minister of Spain and Minister of Finance. She has been a Member of the Congress of Deputies representing Seville since 2019 and, since July 2022, has served as the Deputy Secretary-General and second-in-command of the Spanish Socialist Workers’ Party (PSOE).