Robert, upset by this refusal, left Rome without divulging his programme to the family and went to Naples. At Naples he was lucky to befriended by Lady Anna Carafa. For two years he lived at Norcera trying to complete his education. Lady Anna Carafa wrote to his guardian and prevailed upon him to grant him permission to join the Jesuit Mission. Reluctantly permission was given. At the age of 19, in 1596, he entered the novitiate at Naples where he struck up a lasting friendship with Fabius-de-Fabis.

During the first two years, Nobili's prowess was fully tested. He had to do menial work, and care for the sick. All along he harboured a great desire to go to the east as a missionary. When the opportunity presented itself he offered to go to India. This land with her great tradition and culture held a deep fascination for him. In 1599, Nobili began his “Philosophical” course, during which he studied Logic, Science, Astronomy, Meta-Physics, Psychology and Ethics. It was during this time that his younger brother came of age and Robert was called upon to renounce his title and property in his brother's favour. Robert however, wished to distribute his share of the property to the poor. In 1600, an agreement was reached and out of the disputed property a small sum was allotted to the poor. With great difficulty, he managed to obtain permission from his family to go to India.

In 1603 Nobili left for Portugal. Portugal still exercised control and no missionary could sail to India without the permission of the King of Portugal and that too by a Portuguese ship. On the 28th April, 1604 Robert-de-Nobili left for India accompanying His Excellency Dom Martin Alfonso-de-Castic. The journey was a difficult and hazardous one.

In May, 1605, Nobili arrived in Goa. For the next few months he lived at the college of St. Paul continuing his studies and observing keenly the Indian population. He later moved to Cochin. In 1606 fell seriously ill but recovered. From Cochin, he went to the east, coast where he had to live in a thatched hut. It was here that he began to learn Tamil, from uncouth men