E. De Felice notes that this surname may have as its base the name Genesio or Ginesio, which continues the Latin Christian personal name Genesius, an adaptation of the Greek Ghenésios, derived from ghenésios ("natal, day of birth" and "that protects a lineage, a family"). Alternatively, De Felice points to the place names San Genesio —documented in the provinces of Turin, Savona, Pavia, Piacenza, Bolzano, among others— and San Ginesio, in the Marche region.

E. Rossoni agrees that the surname derives from the medieval name Genesio and specifies its geographical distribution: Genesi is typical of the area between the Piacenza and Pavia areas. The variant Genesin is located in Veneto, specifically in Loreggia, in the Padua area, and in Riese Pio Decimo and Castelfranco Veneto, in the Treviso area. Genesini, for its part, presents two zones of concentration: one in Veneto, in the Verona and Rovigo areas, and another in Emilia-Romagna, around Ferrara and Modena.