A brace from Ilkay Gundogan followed by goals from Bernardo Silva and Sergio Aguero secured City's biggest away in the competition to date and put them in pole position for a place in the quarter-finals.
Raheem Sterling, who has a hamstring injury, is a doubt having not played since the first leg, whilst Fernandinho, who also has a hamstring problem, is also set to be sidelined after limping off in the Carabao Cup final.
Benjamin Mendy has returned to training for City but after a lengthy lay-off is unlikely to return.
Meanwhile, visitors Basel will be without Taulant Xhaka who is suspended, Eder Alvarez Balanta and Germano Vailati will undergo late fitness tests and there could be a return to the starting line-up for Raoul Petretta, Luca Zuffi and Renato Steffen.
As City look certain to be crowned Premier League Champions, their opponents currently sit second in the Swiss Super League having also suffered defeat to league leaders Young Boys last week in the semi-final of the Swiss Cup.
Basel have lost four of their last five games and come into the match with low self-esteem having failed to score in any of their last three.
City come into the game off the back of a 1-0 victory over Chelsea which was their third win in seven days, clinching the Carabao Cup along the way.
City boss Pep Guardiola maintains that his side must remain focused and not make any mistakes against Basel.
The coach has also dismissed claims that his City squad are on par with the Barcelona team that he led to Champions League glory on two occasions.
He stated that his current group of players have only won one trophy under him so far and cannot yet be compared to that amazing Barca side.
Basel manager Raphael Wicky has been disheartened with his team's performances in recent weeks but insists they will bring a positive attitude to tonight's game.
Wicky claims that the game starts at 0-0 and that his side must enjoy this game and give it their all.
· No team has ever overturned a 4-0 home defeat in the first-leg of a Champions League tie.
· Manchester City are unbeaten in their last 12 Champions League home games (W9 D3).
· City have never failed to score in their last 12 European matches.
· Basel have won their last two away games in the Champions League, overcoming CSKA Moscow 2-0 as well as Benfica on a similar score-line.
· Striker Dimitri Oberlin scored one goal in each.
· The Citizens have scored six goals from corners in this season's competition (33% of their overall tally), more than any other team.
· Gundogan has netted twice and assisted two more in his last four Champions League games.
· If Pep Guardiola were to win the Champions League, he would become just the third manager to win the trophy three times and equal the record set by Carlo Ancelotti and Bob Paisley.
Manchester City: Claudio Bravo, Danilo, John Stones, Vincent Kompany, Fabian Delph, Kevin De Bruyne, Yaya Toure, Phil Foden, Bernardo Silva, Leroy Sane, Gabriel Jesus.
Basel: Tomas Vaclik, Michael Lang, Manuel Akanji, Leo Lacroix, Marek Suchy, Blas Riveros, Serey Die, Fabian Frei, Renato Steffen, Raoul Petretta, Dimitri Oberlin.