It is bordered by:
- Viaducto Río Becerra and colonia San Pedro de los Pinos on the west
- Viaducto Río Becerra and Viaducto Miguel Alemán, and colonia Escandón on the north
- Avenida de los Insurgentes and Colonia del Valle on the east
- on the south, colonia Ampliación Nápoles stretches from Calle Georgia to Eje 5 Sur San Antonio; across San Antonio is colonia Ciudad de los Deportes.
Landmarks include the World Trade Center complex with offices, restaurants, cinemas and shopping, and the Polyforum Cultural Siqueiros, a performing arts center decorated with distinctive murals, and an adjacent garden with images of famous Mexican muralists.
One of the original developments here in the late 1930s was Parque de la Lama, designed by Raúl Basurto, one of the principal architects of the Colonia Hipódromo art deco neighborhood further north across what is now the Viaducto. The covenant required buyers to build single-family houses in the "Colonial California" style, (a Mexican term for the California style of Spanish Colonial Revival architecture). Many houses of this style can still be seen in Nápoles. It is also a remarquable spot for architecture of the Mid-century modern style, like the house designed for the recognized architect Vladimir Kaspé in the corner of the streets of Dakota and Nueva Jersey. La Nápoles and La del Valle are the most iconic mid-century neighborhoods in the city. More recently, contemporary apartment buildings have been built as infill, some by Javier Sánchez.
The neighborhood has the Parque Alameda Nápoles (Alfonso Esparza Oteo), a 22,593-square-metre (5.6-acre) park.