Respected this more than I particularly liked it. I'm very happy films like this, ambitious and eccentric, are still able to get into cinemas, but absent that context I found it too messy in tone and the rules of its central storytelling device to work as well as it could have. Specifically, I was never sure what the relationship between Elisabeth and Sue actually was. For much of the film I thought Elisabeth's consciousness moved between bodies during the swap, but despite the repeated 'you are one' mantra, each acted like an individual person and seemed to only discover what the other had done after waking up, raising questions as to why anyone would take the substance to begin with if all it does it generate a de facto entirely new person. If the film's central theme is how women are put under impossible pressure to stay young and sexy forever, having Sue be an independent clone feels less impactful because Elisabeth isn't actually making a sacrifice to make herself younger and sexier in any way: it's more like she's had a daughter of whom she's increasingly jealous.
Like Fargeat's previous film, Revenge, its pretentions to subversion are undermined by how thoroughly it indulges the tropes it puports to be critiquing under a thin veil of irony. Revenge was a supposed inversion of the rape-revenge genre, putting the focus on the strength of the victim and the evil of the perpetrators rather than fetishising the violence against the woman, yet Fargeat still cast a gorgeous lead and had her in a conspicuous state of undress for most of the film. It's much the same here: for all The Substance feigns to damn the male gaze, it lingers over Margaret Qualley's magnificence at every turn, with only Dennis Quaid's hilariously sleazy producer to indicate there's anything exploitative about it, and has her front-and-centre (or, uh, back-and-centre) in the advertising. Don't get me wrong, I'm entirely delighted for any sight of Margaret Qualley under-or-undressed, but in the context of the film it feels more than a little hypocritical.
In terms of tone, the first three-quarters of the film is a sinister, suspenseful body-horror, its satire obvious (sometimes a bit too obvious - did Quaid's producer really need to be called Harvey, rather than leaving it for the audience to make the obvious connection?) but the comedic element kept as subtle seasoning rather than a main ingredient. The end of the film, however, suddenly turns into an overt, grand guignol pulpy spoof, on one hand very funny and possibly the most entertaining part of the film, but a jarringly sharp turn suggesting uncertainty as to how to bring its narrative and themes to a consistent close without relying on splashy spectacle for distraction.
To be clear, this is one of those films where it's easy to focus on the negatives because it took big ambitious swings which didn't quite land and is therefore easier to talk about how it fell short of its ambitions rather than the things it does well. On that score it is visually striking throughout and the key performances are all good, particularly Quaid and Moore (not a role which demands the biggest emotional range, but her commitment is undeniable). Outside Qualley's spectacular aesthetic appeal, hers is the performance I'm least sure about even if I think she's an extremely under-appreciated actress, because she plays Sue as vapidly as the 'character' is underwritten on the page, which could either be seen as a shortcoming or a comment on the obsession with beauty being inherently shallow and materialistic. I like Qualley in it, and she's every bit as game as Moore, but there is a noticeable emptiness to the part, intentional or not.
Fundamentally I think the core issue is how imprecisely-defined the nature of the Substance itself is at any level, which as the story's central pivot makes it hard to get a grip on the angle the film is taking on its themes. There are a lot of strong individual elements in the film but Fargeat never seems entirely sure how to bring them together, reflected in the big tonal shift at the end, fun as it is. Its unashamed weirdness and Cronenbergian horror will attract plenty of fans and for good reason, but for me it was a film defined by what it could have been rather than what is actually is.