From across the Grand Canal it faces the railroad terminal serving as entrypoint for most visitors to the city.

Built in 1718–38 by Giovanni Antonio Scalfarotto, the church shows the emerging eclecticism of Neoclassical architecture.

Wittkower, in his monograph,[1] acknowledges San Simeone is modeled on the Pantheon with a temple-front pronaos, on the other hand, the peaked dome recalls Longhena's more embellished and prominent Santa Maria della Salute church.

The pediment of the entrance has a marble relief depicting "The Martyrdom of the Saints" by Francesco Penso, known as "il Cabianca."

Around the interior of San Simeone Piccolo there are several altar rooms, notorious for minor operas.