The museum is located in some rooms of the former Dominican convent of Santa Croce and Ognissanti, founded in 1566 by Pope Pius V, a native of Bosco Marengo. In the second half of the 19th century, the ownership of the convent passed to the State and it was used as a juvenile reformatory until 1989.

In 1999, the possibility of accessing the funds of the Jubilee of 2000 for the restoration of a part of the former convent, including the rooms originally intended for the sacristy and chapter hall with the purpose of turning them into a museum, was considered. The main nucleus of the museum would have been constituted by the smaller panels belonging to the original altarpiece of the main altar of the annexed church known as the Vasari machine, dismantled in 1712 and replaced by the current main altar.

In October 2011, the museum was inaugurated with the setting up of the first room in which, in addition to the 10 smaller panels of the initial project, the large panel of the "Martyrdom of Saint Peter of Verona" was also added, which had been restored and removed from its previous location in the church. The main nucleus of the museum consists of the panels from the majestic main altar of the church designed by Giorgio Vasari. The paintings were created by Giorgio Vasari himself and his workshop.

In 1712, the altar was dismantled and the paintings that decorated it were variously arranged in the church. The purpose of the museum is to reunite the panels that made up the "Vasari machine," making them more readable in the logic of their original placement.

In 2015, the other rooms were temporarily set up with objects, sacred vestments, and books related to the figure of the Pope who founded the convent, belonging to his family and passed down to the municipality of Bosco Marengo. In other rooms of the museum already equipped, in the near future, paintings and sacred objects, currently being restored or already restored, part of the furnishings of the church and the convent, will be placed.

The museum premises, as well as the rest of the former convent, are part of the state's public heritage and are leased to the Municipality of Bosco Marengo, which manages them in collaboration with the local Association of Friends of Santa Croce; the church and the exhibited works are part of the Fund for Places of Worship (FEC) under the Ministry of the Interior.