I have revised my initial manuscript with a major revision after the first decision. After long months of waiting, I received reviewing results with another major revision. Two reviewers were completely satisfied with my revision and recommended acceptance. One, possibly, new reviewer suggested some improvements but didn't question the novelty of this manuscript. And one reviewer from the previous round said that this manuscript lacks novelty and should be completely revised with new ideas, questions and methods. I don't understand how it's even possible to do that without a completely new, written from scratch, manuscript. Also, we have a comparative literature review and listing what is the novelty in the Introduction and we have comparative numerical experiments in the Simulation section. I don't know if this reviewer advised rejecting because major revision looks impossible. Please, advise on how best to deal with this situation
Based on your comment, I understand that the reviewer doubts the novelty of your work, without specifying details (previous works achieving the same or something very similar as your work).
This kind of feedback is essentially worthless, and should not influence the decision on your paper (if it's a sane editor).
I recommend the following strategy: Systematically address all other reviewer feedback and, based on your revisions, write a strong author response letter. Regarding the criticism of novelty, include a response among the following lines in your response letter:
To our knowledge, our work is the first to achieve X. We discuss the novelty of our work in comparison to related work in section Y of the paper. We would appreciate any pointers to additional works which should be considered in our discussion.