The surname Zambrini presents, according to the main scholars, an uncertain and possibly multiple origin. E. Rossoni notes that it could derive from the personal name Zambrino, documented also in literature, as in the tragedy Galeotto Manfredi by Vincenzo Monti. In this case, the surname would have an anthroponymic origin, arisen from the name of an ancestor that was later transmitted as a hereditary surname.

For his part, F. De Laurentiis proposes a toponymic interpretation, indicating that the surname would be typical of Tuscany and would derive from the place name Zambra (in the province of Pisa). In this sense, the surname would indicate the family's place of origin. In addition, he does not rule out that in some cases it may be related to forms derived from Zanni, which would introduce a possible connection with personal names of wide diffusion in the north and centre of Italy.