McInerney could miss up to 10 weeks after being forced out of the club's two-point win over St Kilda late in the opening half with hamstring tightness.
The in-form midfielder had risen to new heights in injured Errol Gulden's absence, meaning the setback looms as a massive blow for the second-placed Swans (11-2).
Sydney are at least hopeful Gulden - who hasn't played since round one - is on track to make his return from a shoulder injury in round 16.
Key defender Tom McCartin will also be sidelined after suffering another concussion against the Saints, joining Lewis Melican (hamstring), Dane Rampe (calf), Tom Papley (calf), Braeden Campbell (shin) on the sidelines.
Taylor Adams is a test to play after recovering from a hamstring injury and an off-season Achilles tear, and could be an option to cover McInerney - although the veteran midfielder hasn't played at AFL level since round 13 last year.
Fit-again key forward Logan McDonald is a possible choice for coach Dean Cox, having already spent time in the midfield against the Saints as injury cover.
The Swans have already refashioned recruit Jai Serong into a winger, with the former Hawthorn defender kicking the match-winner against St Kilda.
"It's something that's been spoken about, me doing that over the last six months at times," McDonald said.
"I have spent little snippets over there of my career here and there on the wing, but it was probably the first full-blown crack I had at it.
"It helps that we won and I was able to get a little bit of the ball, but I'll just do whatever the coaches need."
McDonald nears his best form after missing all of last season following two surgeries for separate injuries.
The 23-year-old first had an ankle operation after the 2024 grand final loss to the Brisbane Lions, having picked up the injury in the preliminary final against Port Adelaide.
McDonald was on track to make his AFL return in April last year, but suffered a stress fracture in his fibula after just his second VFL match.
He has since put his woes behind him, featuring in all 13 games so far in 2026 and kicking 22 goals to help the Swans sit second behind Fremantle (12-1).
Priding himself on his aerial work, McDonald said rediscovering his confidence has been helped by fellow forwards Joel Amartey and Charlie Curnow.
"Every training session, I pretty much work on it - that's probably the most important thing for modern-day key forwards," McDonald said.
"And I've got two of the best at the club in Joel and Charlie, and then as well going against Tommy McCartin, who's so good at it at the other end of the ground.
"So, flogging myself against them at training is only going to make me better, and I'm starting to see a bit of results now."
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