The Sanctum consistently has a circular skylight with four swooping lines this design has stayed with the building despite the window's destruction on many occasions. The Sanctum Sanctorum is specifically the third floor of the building, home to Strange's meditation room and occult library, where he keeps the Book of the Vishanti, and his repository of ancient artifacts and objects of magical power, such as the Orb of Agamotto. The second floor holds living quarters for Strange, Wong, and any guests they may have. The first floor contains living rooms, dining rooms, and the general library. The basement contains storage, a furnace, and the laundry.

Some are dangerous, such as a radio which is fatal to the touch. The house holds many powerful magical items, some of which have an innocent appearance. Some corridors form labyrinths, and the arrangement of rooms seems to change by itself.

There seems to be more space inside than there would seem to be from outside. 'The outside looks like a townhouse, while past a veil of magical force on the inside are various rooms with various mystical artifacts', as one source put it. The building's depiction has varied over the years but some elements remain consistent. It was noted that as of 2016, the location could be found on Google Maps. In the comics, the building was said to have been built upon the site of pagan sacrifices, and before that Native American rituals, and is a focal point for supernatural energies. It is 'in the heart of New York City's Greenwich Village.' Contrary to fan theories that this address was meant to invoke 221B Baker Street, the fictional domicile of Sherlock Holmes, it was actually a reference to the address of an apartment shared in the 1960s by Roy Thomas and Gary Friedrich. The Sanctum Sanctorum is a three-story townhouse located at 177A Bleecker Street. 177 Bleecker Street, New York City in 2013.

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