The museum was opened on May 13, 2001, by Evangelos Venizelos, then the Minister of Culture and Andreas Sefiha, the president of the Jewish Community of Thessaloniki.

[5][6] The restoration of the building lasted from 1998 to 2003 and was funded by the "Organisation for the Cultural Capital of Europe Thessaloniki 1997".

With the new expansion of the museum, two buildings—the townhouse and the new wing—were attached by arches on their facade to connect as a single portico.

[3] The museum maintains a number of collections: Tombstones from the destroyed Jewish Cemetery, building members from synagogues demolished by the German occupation authorities, religious objects, old and rare books in Hebrew, family heirlooms, ketoubot, public and private letters during the WWII, costumes (19th and 20th centuries), fabrics, tablecloths, books and bank deposit booklets (until 1940).

On the ground level are monumental stones and inscriptions that were once found in the great Jewish necropolis that lay to the east of the city walls.

Central to the first floor is a narrative history of the Jewish presence in Thessaloniki from the third century BCE until the Second World War.