[1] After his return to Italy in 1629, Cardinal Federico Borromeo ordained him canon of San Nazaro in Brolo, a church near the family palace on Via Pantano.

In 1655 Settala traveled to Rome to witness the election of his friend Fabio Chigi as Pope Alexander VII, partially in the hope that papal benediction of his museum would increase its size and prestige; he took advantage of this trip to initiate his relationship with the German Jesuit polymath Athanasius Kircher.

[7][8] Visitors such as the German physicist Ehrenfried Walther von Tschirnhaus, one of the pioneers of porcelain manufacture in Europe, traveled to Milan specifically to meet Settala and discuss his inventions with him.

This will, however, was not carried out ipso facto, for the Canon had many nephews and nieces who had their own views on the matter, one of them in particular, Maria Settala, who had married one of the Crevenna family, refusing to give up what she considered her rights and was only satisfied when she had removed some of the pictures.

It was not till 1751 that Canon Manfredo's legacy was confirmed by a decree of the Senate of Milan, which consigned the collection to the Ambrosian Library, and where 70 years after the testator's death it was duly installed.

The art gallery included several works by prominent Renaissance artists, such as Fede Galizia, Raphael, Brueghel and Leonardo da Vinci.

[13] It contained a full range of natural and man-made items: zoological and mineral specimens; products of the vegetable kingdom; objects from America, Asia, and Africa: silver from Potosí, porcelain from China, Chinese and Japanese texts written in ideograms and Egyptian mummies; weapons; musical instruments; and a significant number of archeological materials and ancient coins.