No, Pokemon will never become unpopular. It's already rooted in a very gigantic base among gamers and non-gamers alike. Look at Mario, he's still going just as strong as ever.
Although I realize that with Pokemon, it is a little more difficult to keep going strong than with the simplicity of Mario. For one thing, there is an ever-growing list of Pokemon. To keep things fresh, they've created Pokemon designed after most well-known species and myths. Eventually they're going to cover all of that, which they basically seem to be doing in Gen 6. They're going to start rehashing ideas a lot, and we're going to get a LOT of Pokemon. It will be harder and harder to collect them all, to memorize them, etc.
I came back into the Pokemon games with Black and white 1 and I didn't realize at how many people were still into it. 7 years ago I haven't heard a thing about Pokemon other than here and there until B&W 1 to be honest.