The two teams have been tipped by many to be fighting for the title come the end of the season so this fixture could give either one the opportunity to portray themselves as the most likely contenders.
City will have plenty of unknowns for their side, such is the difficulty of so-called 'Pep Roulette', meaning predicting their lineup is an almost impossible task.
On the other hand, while Thomas Tuchel is not short of options with plenty of squad depth at his disposal, there's more of a chance of reading into his vision for match day, so here's VAVEL's predicted Chelsea lineup for this weekend's early kick off.
Prior to the Blues' boss' press conference it was more uncertain as to who would be in goal, given the recent injury to Edouard Mendy - which meant backup 'keeper Kepa Arrizabalaga has been in net for the past two fixtures.
UEFA Champions League (@ChampionsLeague) September 24, 2021
However, Tuchel confirmed that the French goalkeeper is 'available and will start tomorrow', which will please fans to no end given his performances over the past year since he signed.
Starting off with the right-sided centre back in the West London side's now famous 3-4-2-1 formation, it seems a surefire bet to predict Andreas Christensen in the position.
The Dane has had an excellent time since Tuchel joined the Blues in January, being part of a European Champions squad and so he'll look to remain in the side after last weekend's win against Tottenham Hotspur.
The 28-year-old appeared close to leaving on multiple occasions under Frank Lampard but has since become one of the first names on the team sheet, so he has to be in the XI.
Finally, to complete the trio at the back, it's the man who opened the scoring in the London derby last Sunday in the form of now 37-year-old Thiago Silva.
Despite what his age may suggest, the Brazilian still looks at the top of his game and is now an integral part of what is becoming a carefully moulded system, so he can't miss out either.
Now, for the sake of simplicity, the two wing-backs have been put in the midfield section of this article, although they of course could be positioned further back depending on the point in the game.
Speaking of the position, at right wing-back Cesar Azpilicueta appears to be the best option for a game like this, with leadership likely more important than youthful energy that may be found with Reece James, thought it's a close call.
Moving across the pitch, next comes the ever-present, ever-energetic and ever-enthusiastic N'Golo Kante who is without doubt always going in the side if he is free from any injuries.
Although physical setbacks have become more common in recent years, when he is fit there is arguably nobody better than the Frenchman, especially alongside someone else in a double pivot.
That fellow colleague will likely come in the shape of Jorginho, who is another player that his seen his career shoot up to standards he himself may not have even foreseen.
The UEFA Player of the Year, after winning European titles for both club and country, is now one of the most respected in the game, and is almost unbreakable alongside the aforementioned Kante.
Something of an outsider in the final few months last season, the 30-year-old has managed to secure his place in the team, and that looks set to continue, despite Ben Chilwell's promising cameos in recent weeks.
To finish up the eleven, attention must first be turned to the two attackers that sit behind the central striker in Tuchel's system - the first of which, on the right, being Kai Havertz.
As his now popular chant goes, he was the man who won Chelsea the Champions League back in May, and is one who now seems to be a regular in the starting lineup, likely meaning he will remain in the side for this weekend's game.
The silky German is just what we need. 🎶 pic.twitter.com/AYSm9evhSu— Chelsea FC (@ChelseaFC) September 24, 2021
Alongside the German is another compatriot of his in Timo Werner, who will look to take advantage of Mason Mount's absence, at least from his own point of view.
He has struggled to be part of the team in the first month or so, limited to mostly substitute appearances, but this game, in which counter attacks could be crucial, may be the perfect fit for the pacy 25-year-old against Pep Guardiola's team.
Last but not definitely not least is the man who will almost certainly lead the line and it's no surprise to see Romelu Lukaku listed in this predicted starting eleven.
The Belgian has had a fantastic (re)start to life in England, already scoring three goals in four Premier League appearances, so it would be astonishing if he was left out against such a tough opponent.
So, that completes the eleven that could be on the team sheet when the sides are announced an hour before kick off, and here it is in all its glory:
Mendy; Christensen, Rudiger, Silva; Azpilicueta, Kante, Jorginho, Alonso; Havertz, Lukaku, Werner
It will undoubtedly be a close-run affair between two sides who are at the very top of European football currently, but with Tuchel's excellent record against Manchester City since he arrived, it's hard to look past a win for the home side, albeit not by a huge margin.
In terms of goal scorers, that too is no easy feat to put specific names onto, but the previously mentioned Lukaku seems to be a safe option, and for the other player to net another Thiago Silva goal isn't outside the realms of possibility.
Chelsea 2-0 Manchester City