Early in the first quarter of Sunday night's clash with Carlton at Marvel Stadium, Wanganeen-Milera clutched his left hamstring as he attempted to burst forward to receive a handball.
The dejected star limped straight down to St Kilda's rooms and later returned with ice on his hamstring before the deflated Saints lost 15.10 (106) to 8.14 (62).
It left St Kilda eight points outside the wildcard places with only games against Richmond and Gold Coast - which they would tackle without Wanganeen-Milera - left.
St Kilda coach Ross Lyon described the 23-year-old's injury as "like an arrow through the heart".
Given a moderate-grade hamstring injury tends to involve at least four-to-six weeks out, it would require St Kilda to pull off a miracle and go deep into September for Wanganeen-Milera to play again this season.
Veteran Mason Wood (left calf strain) is also done for the year.
"It was very disappointing to lose both Nasiah and Mason during the first half of last night's game," football boss Lenny Hayes said in a statement.
"Clearer recovery timelines will be determined for both players in the coming days, however both have clearly been ruled out for the remainder of the home and away season."
The Saints can at least take heart that Wanganeen-Milera's hamstring isn't severe enough to eat into his pre-season.
Lyon said the Saints were "scratching our heads a little bit on the soft tissue" injury given St Kilda had an eight-day break.
The hamstring was on the opposite side to the hip pointer concern Wanganeen-Milera had been dealing with.
But Lyon noted Wanganeen-Milera had missed some training sessions in recent weeks, which was "not ideal" given he was normally a player who always trained.
The Saints are already without Max King (hamstring), Jack Sinclair (calf) and Sam Flanders (achilles)
"Oh, we haven't used it as an excuse to now, and I don't really want to, to be honest," Lyon said.Â
"You've just got to build out a list capable of handling those sort of injuries."
Tom De Koning and Liam Ryan had shoulder injuries scanned on Monday and will be assessed during the week, while Lyon will look to his VFL team for fresh faces.
Lyon believed 11th-placed St Kilda - who recruited hard over the off-season - had been very competitive and their percentage of 101.6 showed it, while acknowledging some might feel they hadn't improved this season.
"But that's OK, I've gotta wear it, I'm fine, I'm a big boy, I'm happy to take what comes," he added.
"But my job - leaders shepherd, protect and nurture and challenge their people under pressure, and that's my job and I'll continue to do it until I'm either tapped or I tap myself."
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