The Gunners boss has led his side to the longest current unbeaten streak in the Premier League - an eight-game run which encompasses the whole of 2020 so far - whereas Man City go into the match off the back of a 2-0 derby defeat to Manchester United at Old Trafford.
However, the Citizens have dominated this fixture in recent years, winning each of the last six meetings by an aggregate score of 17-2, while Arsenal's away form has left a lot to be desired so far this term.
Here, Sports Mole selects its strongest combined XI from the two squads on current form, using only players available for the midweek contest.
Ederson may have something of a point to prove in this match after making mistakes for both goals in Sunday's defeat to Man United, but those were very uncharacteristic and the Brazilian remains one of the very best goalkeepers in the world. Bernd Leno has begun to enhance his own standing with three clean sheets in his last four league outings, but it was a fairly straightforward choice to give Ederson the gloves in this XI.
It is in defence where both sides have had their biggest issues this season, conceding 67 league goals between them, and the back four is duly split evenly with two players apiece.
Aymeric Laporte would be a shoo-in for selection had he been fit, but his absence opens the door for David Luiz to claim a place above Nicolas Otamendi. Both players are prone to rash challenges, but Luiz's recent form has been more assured than that of Otamendi as well as John Stones, Shkodran Mustafi and Pablo Mari.
Indeed, Luiz has kept more clean sheets and made more blocks, interceptions, clearances and successful tackles than Otamendi in the top flight this season, earning his spot at the back.
Luiz's compatriot Fernandinho joins him at the heart of the defence having swiftly established himself as the team's first-choice centre-back in the absence of Laporte, while Kyle Walker at right-back is another simple choice given that Arsenal have had so many problems in that position this season.
Arteta has often been forced to use makeshift full-backs since arriving, although Bukayo Saka has thrived in that role and is chosen in this team ahead of Benjamin Mendy having outperformed the big-money Man City man both defensively and offensively this season.
The 18-year-old has registered more assists, created more big chances, conceded fewer goals and made more blocks and tackles than Mendy despite his usual position being further up the field.
Whereas Arsenal enjoy an even share of things in defence, in midfield it is all Man City. Kevin De Bruyne was the first name on the team sheet regardless of the injury doubt hanging over his head, while Rodri is also an automatic pick ahead of Arsenal's options Granit Xhaka and Matteo Guendouzi.
The main midfield question surrounded who would complete the trio, and Ilkay Gundogan has been the man preferred by Guardiola ahead of David Silva and Phil Foden recently, while he is also preferred in this XI to Dani Ceballos and Mesut Ozil.
Perhaps the most controversial selection in the team sees Nicolas Pepe start ahead of the likes of Raheem Sterling, Riyad Mahrez and Bernardo Silva. While there is little doubt that Sterling in particular, and arguably all three Man City options, have enjoyed better campaigns than Pepe as a whole, on recent form the Frenchman stands above the rest.
Over the last six matches that Man City trio have directly contributed to just two goals between them - one assist for Mahrez and one for Bernardo - whereas Pepe alone has registered three assists and a goal in his last three outings.
The slump in form from City's attackers also makes it an easy decision to select Arsenal skipper Pierre-Emerick Aubameyang on the opposite flank, with the Golden Boot-chasing striker on 17 goals for the campaign including three in his last three.
Aubameyang is the top league scorer from either squad, but Sergio Aguero is not far behind with 16 goals, although he has not added to that tally in four matches since a January purple patch which saw him score six times in three games.
Alexandre Lacazette deserves a mention despite having to play second fiddle to Eddie Nketiah at times recently, although Aguero's main competition came from teammate Gabriel Jesus, who has 10 league goals for the campaign.