It was in Ottoman Egypt, that de Castro rose to great social prominence, especially in official government circles.

He leased the taxes on customs and trade in Alexandria, and in 1520, Selim I, appointed de Castro as master of the mint (mu'allim dār al-darb).

In 1523, Pasha plotted to establish himself as an independent sovereign, and asked de Castro to mint the coins with his name in lieu of the sultan.

de Castro secretly left Egypt and hastened to Constantinople to inform the sultan of Aḥmad's plot.

By the late 1530s, de Castro had moved to Jerusalem, where he played a central role in the city's Jewish society, primarily in its economic life, mainly dealing with real estate.