To put things into perspective, that’s a faster CPU than the Gamebuino Meta, but with a slightly smaller vertical resolution.
2:1 is a bit of an odd aspect ratio.
Personally I like 4:3 the most for handheld consoles, but I’m horribly biased.
Part of what complicates that is that Pico-8 is closed source,
so it’s hard to know what the exact requirements would be,
I suspect there would have to be some cooperation with Pico-8’s creator to have a port to an embedded system.
That said, Pico-8 runs on Raspberry Pi,
so you could just fit a gaming shell around a Pi (possibly even a Pi zero) and use that.
The main page claims that you need a ~700Mhz CPU, but I find that claim somewhat dubious.
I wouldn’t be surprised if there were optimsations that could be done to the source to cut that requirement down.