In 1647, Maidalchini's first cousin,
Camillo Francesco Maria Pamphili, resigned his post as
Cardinal-Nephew to marry and Innocent X required a new Cardinal Nephew. Without any remaining male relative to turn to for an assistant, Innocent X was persuaded to appointed the seventeen-year-old Francesco, his sister-in-law's nephew. Upon being elevated to Cardinal, he was installed as
Cardinal-Deacon of
Sant'Adriano al Foro. Many of the responsibilities of the Cardinal-nephew had been previously delegated to the Secretary of State, Cardinal
Giovanni Giacomo Panciroli, with the military duties assigned to the husbands of the Pope's two nieces. It is possible that the pontiff meant simply to install a relative, however distant, in the Sacred College, without this implying an effective delegation of powers. Without adequate political knowledge for the role, Francesco was assisted by Cardinals Panciroli and
Domenico Cecchini, but he nonetheless remained in a substantially weak political position. The Pope's sisters and other members of the Pamphilj family begrudged his close association with the pontiff and shunned the "adopted" nephew. that in 1650, despite Olimpia Maidalchini's objections, Francesco was replaced by
Camillo Astalli. Although a distant relative by marriage to Olimpia, Astalli had in fact been recommended by his mentor, the Secretary of State. Having blamed Olimpia for his disgrace, Francesco became her bitter enemy. ==Later ecclesiastic career==