From what I've experienced, we use separation of variables when we face linear PDEs and we can safely use them when we're faced with problems that have well-defined coordinates.
For example, in the heat, wave and Laplace's equation, we have the first one depending on space, the second one depending on space and time, and the last one again on space. We can use separation of variables because we make the initial - although implicit - assumption that theses variables are independent in relation to each other. Again, we know how the solutions are supposed to look, so this is a method that works.
There is not a completely settled way of generalizing when you'll be able to use separation of variables. There is a better topic where someone was able to do a good ammount of background check on that matter, which might answer your question: Why separation of variables works in PDEs?