Simone Inzaghi's side trail both Napoli and city rivals AC Milan, both unbeaten and cheek by jowl at the summit, after a series of big matches marked by missed chances and gutting refereeing decisions.
Inter drew their derby with Milan before the international break after missing a penalty and wasting several opportunities to secure a win before a late rally from their rivals almost cost them the match.
Now they host Napoli in front of a sold out San Siro with a chance to claw back some of the ground they lost with their controversial draw with Juventus and collapse at Lazio last month.
Inter come into the clash at the San Siro with an apparent mini injury crisis coming to an end, with Edin Dzeko among those who looked to be out but who should be available for Simone Inzaghi.
They will be missing starting centre-back Stefan de Vrij but Alessandro Bastoni appears to have recovered from the muscle injury which kept him out of Italy's dismal goalless draw with Northern Ireland on Monday.
Napoli meanwhile have an almost full squad available for their trip north, with Kalidou Koulibaly back following his suspension for a red card late last month.
Having Koulibaly back for such a huge match is great news for Luciano Spalletti, who returns to the San Siro for the first time since being replaced by Antonio Conte at Inter in 2019.
Waiting to pounce on either side dropping points are Milan, who travel to Florence on Saturday night to take on a Fiorentina side which have most of their backline unavailable.
Former domestic behemoth Juventus meanwhile sit some 14 points off the pace ahead of their trip to Lazio, who have lost the league's top scorer Ciro Immobile to a calf injury.
Juve also have injury problems as key players again return from their national sides with niggles, with Paulo Dybala, Giorgio Chiellini and Federico Bernadeschi all doubts as they try to stay in touch with the Champions League spots.
Massimiliano Allegri's side are four points behind fourth-placd Atalanta, who kick the weekend off at Spezia.
Player to watch: Victor Osimhen
The Nigeria forward had been going through an uncharacteristic fallow spell until joining up with his country for recent World Cup qualifiers, with his last Napoli goal coming a month ago against Legia Warsaw.
However he netted against both Liberia and Cape Verde over the international break, and although the Super Eagles only scraped into the playoffs for next year's tournament in Qatar, the 22-year-old is back in the goals ahead of Napoliâs trip to Inter.
With Inter missing both Alessandro Bastoni and Stefan de Vrij that can only be good news for the league leaders.
Standout matches today