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Pharo is bootstrapped, and its building process starts with a really minimal image (even the compiler is not included). It is possible to build custom images of any size. You need to take care of packages and dependencies, of course.
Pharo can make applications with a native look & feel - https://github.com/pharo-spec/Spec-Gtk.
Current Pharo has a very solid and powerful FFI, so using C libraries is easy.
The 2008 RoarVM project allowed Squeak to run on a 56 core Tilera chip and was later ported to run on multiprocessor x86 machines:
https://stefan-marr.de/renaissance/
https://github.com/smarr/RoarVM
This was a research project so performance on a single core was poor compared to the official Squeak virtual machine, but it was an interesting exploration of the natural fit between objects/message passing and multiple cores.
What if those already-used tools weren't as-good for writing Smalltalk programs?
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> … its own OS and GUI.
Well there are examples of bare metal Smalltalk (I'm guessing we could say the same of Java?)
https://github.com/michaelengel/crosstalk
I started working on a raylib binding for pharo using pharo's ffi...I have to say pharo's ffi system is very easy to use. It works and I got a few demos working, but I haven't put in the function calls for most of raylib. https://github.com/Zenchess/pharoRaylib
There's also native pharo smalltalk stuff like athens, woden, and maybe others...