In 2024, he achieved his best career major performance by reaching the semifinals at Wimbledon, and won a bronze medal at the 2024 Paris Olympics.

[12][13] After receiving a wildcard and passing the qualifying, he made his ATP Tour main draw debut in February 2020 at the Dubai Tennis Championships, at the age of 17, where he lost in the first round against Andrey Rublev.

[14] In October he received a wildcard for the Forte Village Sardegna Open, where he reached his first ATP semifinal, retiring due to an injury against eventual champion Laslo Đere after trailing 1–4 in the third set.

Musetti was the youngest player to break into the top 100 for the first time in his career by reaching the semifinals of the ATP Tour 500 Mexican Open tournament in March after going through qualifying.

He also beat Frances Tiafoe and 5th-seed Grigor Dimitrov to break into the top 100 and reach his second ATP semifinal, and first at a 500 level, where he was defeated in straight sets by Stefanos Tsitsipas.

He capped off the clay season by reaching the fourth round at the French Open, on his Grand Slam championship debut (only the sixth player since 2000 to do so), beating 13th seed David Goffin, Yoshihito Nishioka and Marco Cecchinato in his first five-set match.

At the end of the season, he took part in the Next Generation ATP Finals, where he was eliminated in the round robin stage as third of his group, having lost to Sebastián Báez[20] and finalist Sebastian Korda, and won to Hugo Gaston.

At the beginning of the season, Musetti reached the quarterfinals at the ATP 500 Rotterdam Open, losing to Jiří Lehečka after having defeated No.

In Monte Carlo, he recorded the second top 10 win of his career by defeating world number 9 Félix Auger-Aliassime in the second round.

[21] After reaching his fourth career tour-level semifinal at the 2022 Hamburg European Open with a win over Alejandro Davidovich Fokina, he made his top 50 debut in the rankings.

[28] He then won his second career title at the Tennis Napoli Cup over fellow countryman Matteo Berrettini, without dropping a set.

From the beginning of the Golden Swing in Buenos Aires, to the Grand Prix Hassan II in Marrakech, Musetti was in poor form, going 2–6 in his singles matches.

At the 2023 Monte-Carlo Masters he defeated Miomir Kecmanović, compatriot Luca Nardi by a double bagel in just 50 minutes,[37][38] and world No.

[41] At the French Open, Musetti played strongly defeating Mikael Ymer, Alexander Shevchenko, and Cameron Norrie all in straight sets, but lost to world No.

[42][43] Prior to Wimbledon, Musetti made two grass court quarterfinals at Stuttgart and Queen's Club; he lost to Frances Tiafoe and Holger Rune respectively.

He also recorded two consecutive first round losses to Grigor Dimitrov at the European indoors tournaments, the 2023 Erste Bank Open and the 2023 Rolex Paris Masters and left the top 25 in the rankings.

He played two doubles matches, both partnering with Simone Bolelli, where he would win one in the round robin stage of the Finals against Chile in September.

[50] He reached his fourth ATP final at the 2024 Croatia Open Umag defeating qualifier Marco Trungelliti, Dušan Lajović and Jakub Menšík[51] but lost to Francisco Cerúndolo in three sets.