Both capped Socceroos were injured in Monday night's costly 1-0 win over Western United.
Nabbout will require knee reconstruction surgery after tearing both his ACL and the meniscus in his right knee.
The 31-year-old's injury is a devastating setback given he had scored two goals in three games this season after much of 2023 and 2024 were ruined by an achilles injury.
"This one's a hard one to take," Nabbout wrote on Instagram.
"Unfortunately I have ruptured my ACL and I'll miss the rest of the season.
"No words can describe what I'm feeling right now, especially after feeling like I was getting back to my best."It's hard to accept, but as I've done time and time again in my career, I'll come back stronger from this."
View this post on Instagram A post shared by Andrew Nabbout (@andrew_nabbout)
Tilio, who is on loan at City from Celtic, will miss the next six-to-eight weeks with a partial tear to his left hamstring tendon.
City are likely to be conservative with a return date for the 23-year-old, who has had a horror run with hamstring and quad injuries over the past two years.
His injury likely effectively rules him out of Socceroos contention until the new year.
City can make an injury replacement signing for Nabbout, if they want, while also having some young attackers on the comeback trail from injury.
View this post on Instagram A post shared by MARCO TILIO (@marcotilio_)
Arion Sulemani (calf) should be back after the international break while Max Caputo (leg) is expected to return within the month from a nasty pre-season injury.
City next play struggling Perth Glory away on Sunday.
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