He coached Piacenza, another Serie B club, from 2004–05 to 2006–07 with good results, including a notable fourth place, only behind Juventus, Napoli and Genoa, in his latest season with the biancorossi.

He was announced in June 2007 as the new Chievo Verona boss for their 2007–08 Serie B campaign and successfully led the Gialloblu to become league champions and promptly mark their return in the top flight.

On 4 November 2008, following an unimpressive start in the 2008–09 Serie A campaign, and two days after a 3–0 loss to Palermo, Iachini was dismissed from his coaching post by the club management.

[5] On 14 November 2011, Iachini was named as the new head coach of Sampdoria, after a disastrous start to the season in Serie B, in place of the sacked Gianluca Atzori.

[6] He charged the team, strongly depressed under the psychological profile and in winter market with radically revised to players motivated and adapted to the category.

On 25 September 2013, he was announced as the new head coach of Palermo, a former team of his as a player, signing a two-year contract and taking over from dismissed Gennaro Gattuso.

During his tenure, he succeeded in turning the Sicilians' fortunes, eventually winning his fourth top-flight promotion, guiding Palermo to be crowned Serie B champions on May 3, five matches before the end of the season.

[19] On 23 November 2021, Iachini returned into management as the new head coach of Serie B club Parma, replacing Enzo Maresca.

[20] On 17 May 2022, after failing to ensure qualification to the promotion playoffs, despite being touted as title favourites before the start of the season, Parma announced their decision not to continue with Iachini as their manager.