Here are four things to consider...
Start for Sterling?
This will be the second of three games in seven days for City, which rightly poses the question, to what extent will Pep Guardiola rotate his squad?
Raheem Sterling was rested for the midweek game against Stoke and given his form, whether or not he returns to the fray is perhaps the most pertinent question of all.
The manager has made it abundantly clear the immediate threat of Middlesbrough is his primary concern, so the appeal of naming the flying winger in his starting XI is obvious.
But there is the finely balanced Champions League tie with Monaco to consider and so Pep may wish to utilise squad depth and bring the likes of Nolito in from the start.
Revamped FA Cup
In amongst his selection and tactical considerations, Guardiola must also contend with FA Cup rule changes.
For the first time there will be no quarter-final replay, meaning this game could go to penalties.
The prospect of a shoot-out could possibly impact on Pep’s substitutes if the game goes to extra-time, when the boss will be afforded an additional fourth sub.
How and whether he uses this is, of course, at his discretion, but it’s sure to be an interesting subplot to the weekend’s fixture.
Attack v defence
The home side’s defensive record belies their 18th placed Premier League position – Boro have the fifth meanest back line in the league, but it’s their profligacy up front which has been their undoing.
You would expect City to enjoy the lion’s share of possession on Saturday, but that is dependent on whether the home side maintain their usual approach.
Clean sheets are most definitely the priority for Aitor Karanka.
However, in a knockout game, free of the concerns of preserving Premier League status and with the defensive trio of George Friend, Daniel Ayala and Calum Chambers all unavailable, might the Spaniard throw caution to the win and decide attack is the best form of defence?
With Stewart Downing and Gaston Ramirez supplying Alvaro Negredo and the powerful Rudy Gestede, Boro could certainly prove to be a handful.
Wembley beckons
It’s been four years since City last played at Wembley in the FA Cup and Guardiola is certainly keen to end the wait.
The impact of such a timely boost cannot be underestimated.
The FA Cup can so often be the catalyst for a fine run of form and while City have certainly been impressive of late, fans and players alike would welcome to the opportunity to head into the tough tests against Monaco and Liverpool buoyed by a confidence swelling Wembley appearance.
