Blanc was The Republicans' candidate for Mayor of Lyon in the 2020 municipal election, in which the list he led placed second before merging with the list of La République En Marche! (LREM) led by Yann Cucherat. He was elected to the municipal council for the 3rd arrondissement. On 4 July 2020, he took office as a municipal councillor and group president in the municipal council. In the 2020 Senate election, he was returned to the French Parliament for Rhône. He later resigned as Wauquiez's deputy.
In the 2021 The Republicans congress, he supported Michel Barnier. In late 2021, he resigned from the group presidency in the municipal council of Lyon following favourable comments he made on Éric Zemmour, which displeased members of his group.