The museum contains one of the most important Pre-Raphaelite collections in the Western Hemisphere,[8] holding some 4,500 pieces of art[3][9] distributed among fourteen galleries.

One of the main features of the museum is its hexagonal galleries, which allow natural light to enter through its corners bringing an illumination to exhibitions.

Pinceladas en Vuelo ("Brushstokes in Flight"), a 28-foot-high aluminum structure created in 1984 by New York sculptor Roy Lichtenstein sits on the front yard of the museum, which was then considered "the largest public [display art] work in Latin America and the Caribbean.

[citation needed] The new 37,745-square-foot (3,506.6 m2) annex to the museum's main building houses an educational space, a library specializing in art history, the Don Luis A. Ferré Archives, a laboratory for the conservation of artworks, an artwork storage area, a museum shop, a restaurant, and administrative offices.

Some of the artists whose paintings and works are exhibited at the museum are Peter Paul Rubens, Lucas Cranach, Bartolomé Esteban Murillo, Eugène Delacroix, and Sir Edward Burne-Jones, among others.

[34] The Last Sleep of Arthur in Avalon, the final masterpiece and crowning achievement of Sir Edward Burne-Jones, is another of the main pieces of the museum's collection, originally acquired by Ferré for just 1,600 British guineas in 1963.

In 2009, both Flaming June and The Last Sleep of Arthur in Avalon were loaned to Tate Britain while the museum underwent a two-year refurbishment.

[36] "Equally important is the Puerto Rican art collection, which ranges from the 18th century to the present day and includes great masters such as José Campeche, Francisco Oller, Miguel Pou, as well as the best contemporary talent such as Myrna Báez, Francisco Rodón, Antonio Martorell and Arnaldo Roche Rabell, among others.

[citation needed] The Museum charges a small admission fee to the public, but most revenues come from substantial donations made by Puerto Rican individuals and businesses.