The botanical gardens were mentioned for the first time in 1615 by the Count of Lemos in his vice royal reform project. But it was not until two centuries later that this idea became a reality. In 1807 a decree by Giuseppe Bonaparte ordered the creation of a "Reale Giardino delle Piante". Work began that same year and lasted a few decades. The garden was finished at the beginning of the 18th century by Federico Dehnhardt under the supervision of Michele Tenore. The Botanical Gardens themselves were conceived as an instrument for the study of plants that could be used for agriculture and commerce. At first plants were ordered according to their scientific classification. This system was soon abandoned. The architectural arrangement (1807-1811) was commissioned to the architect Giuliano De Fazio. He designed the monumental Serra Temperata on neoclassical lines, as is evident from the semi-columns, metopes and triglyphs used in the façade. Thousands of shrubs, herbaceous and arboreous species are cultivated either in the greenhouses (hot, mild or cold) or in the open.

In 1826, Ferdinand Acton purchased two hectares of land from Lord Drummond, land that had originally been property belonging to Drummond's nearby palazzo, and built a villa with a garden there as a summer residence for his family. Pietro Valente was commissioned to do the work, though the owner's personal taste controlled every stage of the project. The villa, of two storeys, was constructed using motifs of a neoclassical style. The garden, which was scrupulously maintained, was designed by Guglielmo Bechi. The residence was sold to the Rothschild family in 1842, and they built a small palazzo, eventually used for offices, in the garden. The interior decoration, designed by Gaetano Genovese, also dates from this period. The residence owes its current name to Don Diego Aragona Pignatelli, duke of Monteleone, who acquired it in 1867. The duke and his wife, Rosina Pignatelli, completely renovated the decorations and furnishings of the villa, which became one of the most important salons in Naples. In 1960, having been donated to the Italian government, the Villa was transformed into a museum.

Constructed during the Fascist era, the Park was restored in 1976. In it are: (a) the tomb of the poet Giacomo Leopardi, created in 1934 in imitation of a Roman funerary column. Until that time, the poet's remains had been kept in the church of San Vitale a Fuorigrotta. The priest of that church had been the only cleric to agree to Count Ranieri's request that he accept the poet's body. Leopardi had died during a cholera epidemic, during which burial in common graves was mandatory. (b) The Neapolitan Crypt, constructed during the Roman era by Cocceius. The Crypt provided a much more rapid link between Neapolis and the Phlegrean Fields than was possible along the hillside routes then available. It is currently unusable because of the collapse of a section of its vault. (c) The tomb of the poet Virgil. It is located next to the Crypt, on some high ground. There is absolutely no certainty that this is the actual tomb of Virgil; but, following ancient tradition, everyone comes here to give homage to the great poet. This is a Roman funerary monument, called a columbarium (a "dove-cote") because of the recesses cut into it. Inside there is a tripod, on which aromatic herbs were burned in honor of