The scholars consulted agree that this surname derives from the place name Nepi, a town in the area of Viterbo, in the region of Lazio, where an old Italian Jewish community existed before being expelled in the 16th century. This toponymic origin is characteristic of many Sephardic and Italo-Hebrew surnames: families adopted the name of the place from which they came or from which they were banished.

E. De Felice characterizes it as a Jewish surname of sporadic presence in Tuscany and central Italy. E. Rossoni adds greater geographic precision, specifying that its distribution is concentrated in the central-eastern part of Tuscany, with an additional presence in the Piceno, a historical area corresponding roughly to the present-day region of Marche. It is also recorded that the town of Nepi itself is believed to have been founded by Jews, a detail that further reinforces the connection between this surname and the Italo-Hebrew tradition of toponymic family names.