From the 14th century, Nuremberg experienced an economic and cultural flowering which reached its zenith during Dürer's time. The city had already been the trade centre of Europe for 200 years and played a leading role in the working of metal and textiles, building instruments, making paper and printing. As the secret "capital of the Holy Roman Empire of the German nation", as it was called in the Golden Bull in 1356, the city attracted numerous scholars and also became the centre of humanism and the fine arts in Germany.

The famous astronomer and mathematician Regiomontanus (1436-1476) called Nuremberg the "centre of Europe." No other city is named so frequently in sources dealing with the economic history of the late Middle Ages. Measures and weights as well as the Nuremberg coinage were points of comparison and reference, and quotes in the Nuremberg market were also used as a starting point for calculating prices in other cities. As an export and import trade centre, Nuremberg was located on one of the two major crossroads of long-distance European trade: amber, salted fish and furs were imported in from the Baltic, the raw materials of the metalworking crafts such as gold, silver and copper from Hungary and Bohemia, valuable silks and luxury items from Venice, and expensive cloth from the Netherlands. Export goods from here such as metal implements and scientific instruments were traded as far afield as Portugal and Poland.

The city was a free imperial city directly subordinate to the Emperor, and enjoyed the privilege of being able to trade duty-free with 70 European cities. Due to its outstanding position in European trade, Nuremberg occupied a strategic position which was also of importance to the ruler. According to law, every new emperor had to hold his first Imperial Diet in Nuremberg. Apart from this, however, the rulers very rarely stayed there. The city council ruled in their absence.

The city's particular significance was further emphasized when, on 24 February 1424, the German king Sigismund brought the so-called "Heiltum" (holy relics), the imperial insignia, crown jewels and imperial collection of relics, together with a document dating from September 1423, for the city to keep in perpetuity. These holy and historical treasures were displayed once a year at the so called "Heiltumsweisungen" on the main marketplace and strongly attracted the public. They were publicly displayed from a "Heiltumsstuhl," a chair like wooden structure about seven meters high. From the Schopperhaus, the gallery with the "Heiltumsstuhl" could be approached via a footbridge. Private displays of the holy relics took place in the Hospital of the Holy Spirit and were restricted to high-ranking visitors.

As a medieval centre of parchment manufacture, the city constantly provided a supply of fine paper to its workshops, publishers and printers. The first German paper mill was erected outside the gates of Nuremberg in 1390. In 1470, the printing trade moved in and was soon flourishing, limited only by the satisfactory supply of paper and metal. Anton Koberger's publishing works rapidly developed into the most important printing business.

Nuremberg occupied a position of supremacy in Europe in the field of metal working, for pioneering innovations in this field such as "Kupferseigerung," the recrystallizing of copper ore containing silver in lead to produce crude copper and silver, had been developed here. So-called "Seiger" commercial companies were set up which appointed factors for purchasing copper ore and selling crude copper and silver to all the important trade cities along the main trade routes. As early as the 14th century, the majority of the craftsmen located in Nuremberg were working in the metal industry. The main export goods, apart from all sorts of everyday tools and metal goods such as nails and needles, were weapons and armor.

Given its outstanding position as a humanist centre, the city gradually gained a monopoly in the production of precision engineered instruments for use in scientific disciplines such as geography, astronomy, mathematics and physics. Nuremberg maps were used on pilgrimages to the holy sites and the cities with great trade fairs. Using instruments made in Nuremberg, Regiomontanus mapped the night sky and calculated the movement of the stars. Inventors such as the Nuremberg master locksmith Peter Henlein introduced devices such as a small portable clock in the shape of a can which chimed and ran for forty hours. Special pieces such as this clock were held in high regard and were ordered in advance by the city council to provide as valuable gifts for important personalities; in the end, they were mass-produced in advance.

During the course of the progressive discovery and conquest of the world, Nuremberg gradually lost its monopoly as the capital of European trade, for the geographical emphasis had shifted in favour of the western European seaports. The importance of the city diminished, in particular as Nuremberg merchants did not play a part in discovering and investing in the New World.