Before 2004, lists could be presented only at the departement level, allowing smaller parties (notably Hunting, Fishing, Nature, Tradition, Alsace d'abord, Lutte Ouvrière, Revolutionary Communist League) to be represented as such in the regional councils and thus forcing major parties to enter into negotiations to rule some regions.

Following the 1999 and 2003 electoral reforms, with a first implementation in 2004, a two-round runoff voting system is used to elect the regional presidents.

When National Rally MEP Jordan Bardella tweeted criticism of Muslim LREM candidate Sara Zemmahi for wearing a hijab in a campaign poster, Executive Officer of La République En Marche!

Guerini claimed that "wearing ostentatious religious symbols on a campaign document is not compatible with the values of LREM".

Three of them (Xavier Bertrand of Hauts-de-France, Laurent Wauquiez of Auvergne-Rhône-Alpes and Valérie Pécresse of Île-de-France) were seen in the case of victory as potential contenders of presidential elections of 2022.

Before the elections, pundits discussed the possibility of the National Rally winning a region (Provence-Alpes-Côte d’Azur), but they failed to do it and underperformed compared to their polling.