[1] Named after her paternal grandmother, Margherita was baptized on 11 January 1568 with her godparents being Pope Pius V (represented by Bishop Ferdinando (Ferrante) Farnese –a distant cousin of the Latera branch of the Ducal family[2]) and her paternal great-grandmother Gerolama Orsini, Dowager Duchess of Parma (represented by Caterina De Nobili Sforza).

The Crown Prince's secretary, Dr. Marcello Donati, reported this to Duke Guglielmo of Mantua, citing a congenital "obstruction" [narrow vagina] in his son's wife as the cause of the problem.

[3][8][9] In Mantua, where the newlyweds solemnly entered on 30 April 1581, the princess was examined by another doctor, Giulio Cesare Aranzio, and also proposed to remove the obstacle by artificial means.

Carnival of 1582 was held by the Hereditary Prince and Princess in Ferrara, where they stayed with Duke Alfonso II d'Este and his wife Margherita Gonzaga, Vincenzo's older sister.

Duke Guglielmo of Mantua, wishing to continue the dynasty, began to insist on the artificial intervention, otherwise, he threatened with divorce.

In Parma, she was examined by doctors again, including Andrea Marcolini da Fano, personal physician to Cardinal Alessandro Farnese.

In February 1583, the Cardinal arrived in Parma, where, after listening to the opinions of doctors and interested parties, he persuaded the Hereditary Princess to abandon the operation and follow him to Milan.

Before agreeing to the marriage, the House of Medici humiliated Margherita's ex-husband: Vincenzo had to prove his virility in front of witnesses by having sexual intercourse with a virgin maid.

Her monthly allowance of 150,000 gold scudi was paid irregularly so that she couldn't use it to bribes in order to establish communication with her alleged lover, who was imprisoned at that time.

[3][13][14] In December 1592, Margherita's brother Ranuccio I Farnese became in the new duke of Parma; he immediately transferred her to the monastery of Sant'Alessandro and hardened the conditions of her detention.

In the following years, Margherita indirectly participated in the court life in Parma, speaking in defense of her two nephews, the illegitimate children of Duke Ranuccio I: a daughter, whom she accepted in her monastery and veiled into a nun with the name of Sister Maura Margherita, and Ottavio Farnese, whom she tried to rescue from the prison in which he was imprisoned by his own father because of his participation in a conspiracy.

In 1616 she intervened, supported by financial aid offered by the devotees, in order to complete the Franciscan church of Santi Gervaso e Protaso, now dedicated to the Santissima Annunziata, according to the plans by Giambattista Fornovo.

[3][17] The Margherita's tomb is located next to her father's; on the tombstone are carved the coat of arms of the House of Farnese and an epitaph with a summary of her life.