In 1702 Nieto succeeded Solomon Ayllon as ecclesiastical chief of the Portuguese Jews in London; and two years after his settlement in that city he published his theological treatise, Della Divina Providencia, ó sea Naturalezza Universal, ó Natura Naturante (London, 1704).
He explained that 'nature' was a modern word, and in reality referred to the action of God in governing natural phenomena.
In his Matteh Dan, or Kuzari Heleq Sheni (London, 1714), written in Hebrew and Spanish on the model of the Kuzari of Judah ha-Levi, he defended the Oral Torah against the Karaites, and showed that the disagreements in the Talmud lay not in essential laws but in minor matters.
Nieto was one of the most accomplished Jews of his time and was equally distinguished as philosopher, physician, poet, mathematician, astronomer, and theologian.
A prolific writer, his connection with Christian scholars was extensive, especially with Ungar [cs], the bibliographer.