Cantalupo nel Sannio is a town and comune in the province of Isernia, in the Molise region of southern Italy.

The town was known simply as Cantalupo until February 4, 1864, when the denomination nel Sannio was added in order to differentiate it from other villages with the same name. The specification of nel Sannio is derived from the fact that the village is located in the ancient territory of Samnium, which was inhabited by fierce Italic tribes known as the Samnites, famous for their resistance of Roman domination in the Samnite Wars. The name Cantalupo is thought either to derive from the Greek "Kata-Lupon", "in the middle of the woods", or from the Bulgarian "Kan-Teleped", meaning "chief residence". The latter explanation is favoured due to the well-established Bulgarian presence in the territory of Samnium going back at least to the 7th century.