Let $L$ be a countable language. Let $T$ be a complete $L$ theory. We know that if $T$ is small, then there is a prime model of the theory. But $\text{Th}(\mathbb{N},+,\times,0,1)$ is not small but it has a prime model.
As far as I'm aware there is no necessary and sufficient condition for the existence of prime models. But I would like to see how to show certain theories do not have prime models. For example, how would you show that any consistent extension of ZFC doesn't have a prime model? (I strongly suspect that is the case).
Edit 1: To clarify: I'm asking if there is a "standard" argument that you can try when you suspect a theory doesn't have a prime model.
There is a simple necessary and sufficient condition for the existence of a prime model: "isolated types are dense". If $T$ is a complete theory in a countable language, then
These facts should be proven in every model theory textbook - they're Theorems 4.2.8 and 4.2.10 in Marker, for example. The situation is more subtle if $L$ is uncountable (largely because it's harder to omit types), and I suspect there's not a satisfying general criterion for the existence of prime models in that context.
One more comment: To prove that $T$ does not have a prime model, you need to come up with a formula $\varphi(\overline{x})$ which is not contained in any isolated type. This means $[\varphi(\overline{x})]$ is a perfect set in the Stone space, so there must be continuum-many types containing $\varphi(\overline{x})$. This is why small theories have prime models.