In the 2008–09 season, Gasperini led Genoa to fifth place of Serie A, the highest placement for the team in 19 years, thus securing a UEFA Europa League spot, relaunching players like Diego Milito and Thiago Motta in a 3–4–3 formation and a particularly spectacular football style that was praised throughout Italy,[5] so much so that José Mourinho, manager of Serie A champions Inter Milan, stated Gasperini was the coach who put him in greatest difficulty.

[6] However, a poor start in the 2010–11 season, with 11 points in 10 games despite popular signings such as Luca Toni, Rafinha, Miguel Veloso and Kakha Kaladze, caused Gasperini's dismissal from his coaching post on 8 November.

[19] His first season in charge turned out to have a difficult start, Gasperini being on the verge of sacking after five rounds which saw Atalanta in the penultimate place after a 0–1 home defeat to Palermo.

However, from there on the team's results steadily improved, leading them to beat Inter, Roma and Napoli, with a streak of six consecutive victories in Serie A leaving them in sixth place during the winter break.

The following season, returning to Europe after 26 years of absence, Atalanta managed to win their Europa League group that also included Lyon, Everton and Apollon Limassol, remaining undefeated to progress to the round of 16, where they were eliminated by Borussia Dortmund after a 1–1 home draw and a 2–3 away loss in Germany.

In Serie A, they managed a seventh place finish, thus earning another UEFA Europa League qualification, this time in the second qualifying round, while in the Coppa Italia they progressed to the semi-finals, where they were eliminated by Juventus.

Atalanta qualified for the round of 16 of the Champions League for the first time after finishing in second place in the group that also included Manchester City, Shakhtar Donetsk and Dinamo Zagreb.

[24] Despite the impact of the COVID-19 pandemic in Italy, which struck Bergamo severely, Atalanta finished in third place in Serie A once again in 2020, qualifying for the Champions League for the second consecutive season.

"[37] On 24 April Gasperini led Atalanta to overturn a 1–0 deficit from the first leg of the Coppa Italia semi-finals, eventually beating out Fiorentina 4–2 on aggregate to advance to the final against Juventus.

[43] On 22 May, he achieved his first career title, as he led Atalanta to their first-ever European trophy, following a 3–0 victory over German champions Bayer Leverkusen in the Europa League final.

As such, at times his trademark 3–4–3 system resembles a 3–4–1–2, 3–2–4–1, 3–5–2, or 3–4–2–1 formation, with energetic overlapping attacking wing-backs in lieu of wide midfielders, that provide width along the flanks and push up the pitch when going forward.

During the 1990s, Gasperini's tactical philosophy and teams' playing styles was inspired by Dutch football, namely Louis van Gaal's Ajax side, rather than Arrigo Sacchi's 4–4–2 system, which first led him to switch from a four to a three–man back-line.

When defending off the ball, his teams are also known for the use of heavy pressing, but also apply elements of fluid man-marking across the entire pitch and often switch to a 5–4–1 formation defensively.