I couldn't find the POSIX specification for cc(1).

No surprise, because cc is not part of the POSIX-defined utilities. c99 is. (with respect to the latest POSIX 1003.1-2017 standard)

Aside from that, without specifying which C/C++ (i assume) compiler(s) and which compiler versions your Q is about, one has to assume your question is about any C/C++ compiler. The probability that all C/C++ compilers in all (recent-ish) versions made available to the public (or to be made available in the future) feature the -isystem option exhibiting the expected/desired behavior is approaching zero. (And you would only need to find one single compiler not having an -isystem option or having one with a diverging behavior for the probability to become a perfect zero). On the other hand, if your Q is meant to ask about some specific compilers only, you could quite easily and very quickly determine whether the compilers of interest have such an option by simply looking up their documentation/man pages

Hmm, interesting. I'll copy here a link to the c99(1) specification for completeness: https://pubs.opengroup.org/onlinepubs/9699919799/utilities/c99.html.

My question was about portability to Unix systems, including systems about which I don't know much, such as Solaris or HPUX for example. If a weird Windows compiler doesn't like the option, okay, but if a Unix compiler doesn't, that would be a problem for me.

[...] but if a Unix compiler doesn't, that would be a problem for me.

Well, you already linked the POSIX standard for c99. Does it feature an -isystem option? And if c99 is not required by the POSIX standard to have an -isystem option, would it be a problem for you if some POSIX-compliant c99 on some Unix-like platform does not implement -isystem? If so, you need to stick with the compilers that support this option. Don't worry about unknowns. Instead, make it an explicit requirement which compiler(s) shall/can be used to build your project(s). (like -almost- everybody else is doing...)