Walter Mazzarri's side have only taken two points from five Serie A games in 2014, meaning December's derby victory over Milan remains their only win in 10 league matches.
Milan are also the only team Sassuolo have tasted victory against since November 24.
Alberto Malesani's first game in charge ended in a 2-1 defeat against Verona last Sunday, and Sassulo's new coach has only overseen three victories in 18 previous meetings with Inter.
The reverse fixture saw Inter record their biggest win of the campaign to date as Diego Milito scored twice in a 7-0 win.
And despite their recent poor form, Inter go into this weekend's game having lost just once at San Siro this season.
Goals have not been flowing recently, though, with the club finding the net just twice since the turn of the year.
Sassuolo have claimed just one away victory this season - a 4-3 triumph at Sampdoria on November 3 - and head into Sunday's game 19th in the table after three consecutive losses.
Domenico Berardi is likely to be central to any upset against Inter, with the 19-year-old having scored four goals against Milan and 12 in 17 Serie A appearances.
Victory over Milan on January 12 lifted Sassuolo out of the bottom three, but they have dropped back into trouble and now occupy their lowest position in the table since the end of October.
New Inter signing Hernanes is expected to make his debut after a deadline-day move from Lazio.
The Brazilian is likely to replace Ricky Alvarez, who has been ruled out with a thigh injury.
Pedro Mendes is suspended for Sassuolo, who must also cope without Emanuele Terranova and Marcello Gazzola.
