After a short period in his native town, he settled in Naples. In this city he opened a school of Literature and Philosophy. He soon earned the esteem and affection of distinguished personages, among them the servant of God Joseph-Maria Pignatelli of the Society of Jesus.

 When the Neapolitan Revolution of 1799 broke out, Don Francesco made the decision to leave Naples and returned to the country. In Mugnano del Cardinale, he devoted himself to ministry and promoted, together with other confreres, missions in the Naples area and in the south, bearing copious fruit for the people of God. This apostolic lifestyle earned him the esteem of many Neapolitan personalities, which prompted Bishop Bartolomeo De Cesare to be accompanied to Rome  to receive episcopal ordination by Pope Pius VII on June 30, 1802. It was on this occasion that in Rome he came into possession of the body of Saint Philomena through the mediation of De Cesare himself. Divine Providence had prepared this trip so that, Don Francesco De Lucia, would become the promulgator of the cult of Saint Philomena. Soon, in fact, he became the historian of her relics, printing in 1824 the "Relazione Istorica della traslazione del Corpo di Santa Filomena da Roma a Mugnano." The work quickly spread to every city in Italy and was translated into several languages. The first edition of 1824 was followed by others; as many as six editions were revised and corrected until 1843.

 With the purpose of giving the cult of the young Martyr stronger and deeper roots, Don Francesco De Lucia founded in Mugnano the Pious Association of the "Virgins of St. Philomena," also called "The Nuns of St. Philomena." Many people, mostly young people, housewives or peasants joined the religious-laity institution founded by the pious guardian of the shrine. These lived with their families, distinguishing themselves by their deep devotion to religious life. They wore a black dress, a white veil and a small crucifix on their chest and observed the simple vow of chastity by the exercise of pious daily practices. The dedication of these Pious Virgins meant that this institution, conceived by Don Francesco De Lucia, soon spread throughout the Kingdom of Naples and France. Many bishops and prelates requested and adopted the Rules of the Nuns of Saint Philomena, written by De Lucia for their Religious Institutes.

 Fr. Francis earned the esteem of Pope Leo XII, bishops, priests, religious, and august personages such as Ferdinand II King of Naples, who honored and respected him. Until 1843 King Ferdinand II visited the shrine no fewer than 25 times, both with his first consort Maria Christina of Savoy and his second consort Maria Sophia. Finally he earned not only the veneration of his fellow citizens, but especially that of the Saint's devotees.

 On Good Friday in 1835 Don Francesco De Lucia, on his way to Nola to greet the bishop, fell off a donkey. That fall was the beginning of a long infirmity. Despite his infirmity, in the years when cholera broke out (1836 - 1837) in Mugnano del Cardinale, the venerable priest became a consoling angel to all the sick and dying. On April 14 in 1941 he had a second fall. In 1845 another fall caused him to rupture an artery that made him infirm and brought the pious priest severe pain. During these years of infirmity he bore his illness with edifying and heroic endurance and a desire to continue in his work.

After devoting 41 years of his priestly ministry to the continued service of the Shrine and the spread of the cult of St. Philomena, Fr. Francesco De Lucia, at the age of 75, rendered his soul to God on April 9, 1847. The loss of the custodian of the Sacred Relics of St. Philomena was a profound mourning for the town of Mugnano del Cardinale and for the Saint's devotees; the solemn funeral rendered to him at the Shrine was a clear manifestation of their love for the Shrine's custodian.

 During the days of the funeral, security guards were needed to prevent the crush of the surrounding people, who flocked to pay their last respects to the venerable custodian, trying to obtain a shred of his robes to keep as a relic. The eulogy was delivered by Dr. Don Nicola Sirignano, who was bound to De Lucia by deep esteem and friendship.

 As the funeral rites were to take place, the body was placed before the Saint's chapel, some wished that candles be lit at the Saint's altar, and that the bell-wheel be rung, as is traditional, just as it happens in the ceremony of the removal of the veil covering the urn with the sacred body of Saint Philomena; but others objected, and the latter, prevailed. But as the porters lifted the body for the public obsequies, the bell wheel, without anyone moving it, prodigiously began to ring to the amazement of the clergy and people present. The candles were then lit and the veil covering the urn with the Body of Saint Philomena was lowered. Don Francesco De Lucia was provisionally buried in the "chapel of the Congregation of the Immaculate Conception, near the parish church".

To preserve the memory of this fervent servant of God, Marquis Alfonso d'Avalos of Vasto and Pescara, Superintendent of the Shrine, erected a memorial to the left of the nave of the Shrine. The body of the founder of the Shrine on December 9, 1848, with solemn funeral pomp, subject to an act of recognition by the Curia of Nola, was moved and placed in the funeral monument.