Regarding this question on when to ask about a manuscript's status in review I wonder (since it is happening to me): What does it mean when a paper is "with editor" for two months after a first review?
So, after the first round of review, you were asked to revise your manuscript extensively. And you made changes accordingly and resubmitted a revised version. Two months has passed since then, but it doesn't seem like the revised manuscript has been sent out for external review because the status of your submission you can see online hasn't been changed and is still "with editor." (Edit: I know some journals use "being handled by editor" or something similar at any stage of the review process except when the manuscript is with the author. You're sure it wasn't "with editor" during the first round review, right?)
If that's the case, most likely it means the editor is having hard time finding referees for the second round or maybe simply taking their sweet time examining your resubmission. Or possibly they forgot about your submission so you need to remind them.
I don't know what the norm is in your field. But if I were you, I'd send a short and polite email to the journal to ask what is up with your paper, probably after waiting a bit more. If it doesn't work, I'd send another polite email to someone else working for the journal. In any case, you should understand that the editor is a volunteer (unless you're submitting to a journal with fulltime editors like Nature, Science, PRL etc.), and sometimes it takes a while to handle your submission for various legitimate reasons. So be polite when asking what's going on.
Edit: And the best way to know if two months is too long is to ask experienced researchers in your field like your advisor if you're a student.
There's no way to know for sure except to ask the editor.
If you mean that the editor received the first review from a referee two months ago, it may be that the editor has not yet decided what to do with the paper, based on the review. Another possibility is that the editor wants a second review, and has not yet found a referee for it.
It most likely means that your manuscript is undergoing a second round of review, after you made revisions to it. In most fields, two months is not overly long time to wait for reviews, especially if you made large modifications to the manuscript, or if the editor is not sure what to do and asked for an additional referee’s opinion (or adjudicating referee, in some cases).
You can, however, write a nice email to the editor enquiring about the status of your manuscript.