I suspect that colonizing Mars (or wherever else) will turn out to be much more than just an engineering problem. If we get things like food, water, atmosphere, and even gravity right, I think we’ll still find an endless list of requirements that we didn’t know were requirements… and some mystery problems that don’t seem to have any cause at all. Those problems will be because of factors we never thought of, or don’t even know how to detect.
There could also be surpluses/deficiencies in our diet or environment that will take years (or perhaps generations) to show up. Again, that would be because of unanticipated, and maybe unsolvable, problems.