In 1494, King Charles VIII of France bought a portion of the ancient Gardens of Lucullus from the papal scholar and former Patriarch of Aquileia, Ermolao Barbaro.

In 1502, Louis XII of France began construction of the church of the Trinità dei Monti next to this monastery, to celebrate his successful invasion of the Kingdom of Naples.

The architect of the facade is not known for certain, but Wolfgang Lotz suggests that it may have originated in a design by Giacomo della Porta (a follower of Michelangelo), who had built the church of Sant'Atanasio dei Greci, which has similarities, a little earlier.

[5] The inscriptions found in Santissima Trinità dei Monti, a valuable source illustrating the history of the church, have been collected and published by Vincenzo Forcella.

[5] In the fourth chapel, the Cappella Orsini, are scenes of the Passion of Christ by Paris Nogari and the funeral monument of Cardinal Rodolfo Pio da Carpi by Leonardo Sormani.

The second chapel on the left has a well-known canvas of the Deposition by Daniele da Volterra; flanking it are frescoes by Pablo de Céspedes and Cesare Arbasia.

In a niche along a corridor that opens onto the cloister is the fresco (reputed to be miraculous) of the Mater Admirabilis, depicting the Virgin Mary, painted by Pauline Perdreau, a young French girl, in 1844.

By the Diplomatic Conventions of 14 May and 8 September 1828 between the Holy See and the Government of France the church and monastery were entrusted to the 'Religieuses du Sacré-Coeur de Jésus' (Society of the Sacred Heart), a French religious order, for the purpose of educating young girls.