My feeling sadly is because uv is the new thing, it hasn't had to handle anything but the common cases. This kinda gets a mention in the article, but is very much glossed over. There are still some sharp edges, and assumptions which aren't true in general (but are for the easy cases), and this only going to make things worse, because now there's a new set of issues people run into.
PEP 751 is defining a new lockfile standard for the ecosystem, and tools including uv look committed to collaborating on the design and implementing whatever results. From what I've been able to tell of the surrounding discussion, the standard is intended to address this use case - rather, to be powerful enough that tools can express the necessary per-architecture locking.
The point of the PEP 723 comment style in the OP is that it's human-writable with relatively little thought. Cases like yours are always going to require actually doing the package resolution ahead of time, which isn't feasible by hand. So a separate lock file is necessary if you want resolved dependencies.
If you use this kind of inline script metadata and just specify the Python dependency version, the resolution process is deferred. So you won't have the same kind of control as the script author, but instead the user's tooling can automatically do what's needed for the user's machine. There's inherently a trade-off there.
