I'm not an expert in any of Metamath, Isabelle (Isabelle/ZFC or otherwise) or Mizar, but I did some research on this topic when Hamster asked me essentially the same question a couple of days ago. So here's an attempt at an answer, to get the ball rolling.
The use of meta-variables in Metamath is the fundamental concept that enables it to verify proofs, and it is independent of the "object logic" with respect to which you want to prove theorems. So Metamath's architecture (meta-variables, substitution) is not a formulation of ZFC or any other logic. It's just a business of substituting well-formed formulae for metavariables, and applying axioms.
As Thierry Arnoux pointed out, the use of meta-variables makes it possible to define axiom schemas AKA axiom schemes.
In Isabelle, meta-variables are referred to as "schematic variables". This is a generic term, not restricted to Isabelle: https://en.wiktionary.org/wiki/schematic_variable
(The Isabelle manual notes that schematic variables are called "logical variables" in Prolog.) Now, unlike in Metamath, a proof in Isabelle doesn't proceed by substitution of terms for meta-variables, so while meta-variables are available, they aren't the foundation of the system.
In Mizar, the problem of expressing axiom schemas arises as well. The approach taken in that system is to support free second-order variables, in addition to the first-order logic that the system manipulates.
Freek Wiedijk writes:
Mizar is based on first order predicate logic. However first order
logic is slightly too weak to do ZF-style set theory. With first
order logic ZF-style set theory needs infinitely many axioms. That’s
because ZF set theory contains an axiom scheme, the axiom of
replacement.
(From https://www.cs.ru.nl/~freek/mizar/mizman.pdf)
In practice these second-order variables are written as letters followed by terms in square brackets (for predicates) or parentheses (for functions).
So Mizar and Isabelle both make it possible to express axiom schemas, using schematic variables or second-order variables, respectively, whereas Metamath is entirely founded on the principle of meta-variables and substitution: that's Metamath's trick.
According to Raph Levien, the minimalistic Metamath style works out in practice to be similar to the "Little Theories" approach. https://www.researchgate.net/publication/2614291_Little_Theories
That doesn't explain why Metamath's approach is powerful enough to do what it does, but maybe it sheds some light on the philosophy behind it.
$a
axiom statement in set.mm. I don't have the necessary background in Isabelle/ZFC and Mizar to comment about the difference with them. $\endgroup$