The activities for institutional preserving and presenting of the historical and cultural heritage in Prilep had started in the period after Word War II, with the forming of the National Museum in 1955. At the beginning, in the framework of the National Museum, also functioned the Museum of NOB that became the Memorial museum “11 th of October 1941” and is still part of the institution. Even in the first years of existence of the National Museum was formed a workshop for protection and conservation interventions, and a photo laboratory which are important components in the work of the institution.

In the framework of the National Museum in 1957 was formed the first Colony of painters in Macedonia, and in 1963, the symposium for sculptors “Marble”. Later, in 1974 was formed the International studio for wood sculpting. In addition, because of the intensified research works in the field of archaeology in 1961 in the framework of the National Museum was placed the Permanent archaeological exhibition set. In 1973, the National Museum with the forming of a Museum for tobacco had started collecting objects for consuming and processing of tobacco, documentation, paintings and sculptures from that field.

In the National Museum-Prilep from 1979 entered the Memorial museum “Kuzman Josifovski-Pitu” with permanent exhibition dedicated to the person and the deeds of the national hero.

Originating from the National Museum Prilep, the Institute for research of the Old Slavonic culture and the Center for Contemporary art, that contains an exceptional collection of works of art from artists from all around the world, were formed as separate institutions in 1980.

In 1981 the National Museum – Prilep was transformed into Institute for protection of the cultural monuments, natural rarities and Museum. The institution develops the following scientific disciplines: archaeology, history, art history, ethnology, architecture and had created museum collections with a vast number of exhibits. A big number of exhibitions and cultural manifestations, and scientific-research and conservation projects had been realized. In addition, the institution has an internal library, rich book fund with more that 1900 books, 1536 magazines and reference literature that consists of 132 dictionaries, encyclopedias and lexicons.

With the opening of the Icons Gallery in 2002, the Institute and Museum Prilep is increasing the number of its permanent museum set where there are exhibited 66 icons and other objects from the churches and monasteries of the wider Prilep region.