Frêche gave her important responsibilities such as finances, municipal staff, legal affairs since 1995, and vice-mayor from 2001. She became mayor of Montpellier in 2004, following the resignation of Frêche, who could not cumulate the job as mayor with his new role as President of the Languedoc-Roussillon Region. Despite being close to Frêche in the past, she has recently distanced herself from him following his notoriously controversial remarks.
On 28 January 2010, following controversial comments made by Frêche about Laurent Fabius, Martine Aubry asked Mandroux to form a list supported by the party for the 2010 regional elections.
Her list received the endorsement of the Personal against Frêche"s dissident list, but did not prevent Frêche from retaining the presidency of the region.