The Italian initially joined Chelsea as a player from Lazio in 1996 and scored 26 goals in 175 appearances for the English club, before returning as Andre Villas-Boas' assistant coach in 2011.
Di Matteo took on the top job on a caretaker basis after Villas-Boas was sacked in March 2012 and guided Chelsea to UEFA Champions League and FA Cup glory.
It did not work out for Di Matteo after he was appointed permanently, though, and his sacking in November 2012 was considered premature and harsh by many.
After almost two years on the sidelines, Di Matteo returned to management last month to replace Jens Keller at Schalke.
And he has the chance to pit his wits against Chelsea in the cauldron that is the Veltins Arena, with Schalke aware that they can move to the top of Group G with victory.
The German side cannot assure their last-16 berth in this game, nor can they be eliminated, but Chelsea can secure their progression with a win or any draw in which they score two goals or more.
Di Matteo's side ended Wolfsburg's six-match winning streak in the Bundesliga on Saturday, with Eric Maxim Choupo-Moting's on target twice in a 3-2 home triumph.
"We played very well. We played confidently, didn't let ourselves be intimidated and we've been working very hard in training these past two weeks, which helped us today," Choupo-Moting is quoted as telling the Bundesliga's official website.
Schalke, who sit second in the pool, have won four of their seven matches under Di Matteo.
Chelsea delighted manager Jose Mourinho with a "beautiful" performance in their 2-0 Premier League win over West Bromwich Albion on Saturday.
Diego Costa and Cesc Fabregas played key roles for the league leaders after sitting out international duty with Spain due to hamstring problems.
Costa and Eden Hazard scored for a Chelsea side who have not lost a competitive match since Atletico Madrid beat them in the second leg of their Champions League semi-final last term.
Mourinho played down talk that Tuesday's clash would be dominated by the respective managers and told reporters: "This is a match between Chelsea and Schalke and not Di Matteo and me.
"We need to get enough points in these last two matches to get through to the last 16. If we lose both matches we go into the Europa League.
"This team wants to be a very good one, and so they want to play against the best teams in the best competition, so I would feel very frustrated if we have to go to the Europa League."
Schalke have not beaten Chelsea in five previous Champions League matches, scoring only one goal in the process.
That goal came in this year's competition, though, as Klaas-Jan Huntelaar cancelled out Fabregas' early strike in a 1-1 draw on matchday one.
Chelsea played Schalke twice in last year's group stages, winning 3-0 on both occasions.
