Ahh..so even a curb stomp by the Persians wouldnt reverse their fortunes Empire-wise?
The Persians? They'll reform as a new Empire soon enough, probably not a Neo-Achemenid Empire, but perhaps one built around Mesopotamia, or someone else. I'm not aware of what other major military powers were interested in Persia at the time.
Alexander the Great has only recently quietened Greece. They still have the extra manpower that he called upon during his campaigns. Will Alexander try to fight another Guagamela? Perhaps, and he may win it.
But really, the way I see it is that Alexander humbled WILL NOT go to Mesopotamia, not into Persia-Proper. He is certainly interested, but he wouldn't have the manpower, or the ego after being crushed at Gaugamela, and losing so many generals.
I can see a few major conquests that could still happen.
1) Anatolia, Levant and Egypt - If Alexander goes East, these are the easy conquests, especially if he wins a 2nd Gaugamela. It isn't Persia Proper, so it can still be sold as Liberation, and isn't going to be a powerbase for a Persian Satrap.
2) Anatolia (again), and the Euxine Sea - This is still the General who defeated the Steppes - the Euxine Sea would be a lovely addition to his Empire. Again, not Persia Proper.
3) Illyria/Dalmatia - This could be an interesting conquest that is much more similar to home. If he can rule from The Danube to the Coast, he's created an Empire that could easily hold out again the Galatians/any other tribes that are coming this way.
4) Dacia - Close to home, defensible, and an interesting addition. It provides security for the Danube, and opens it up for Greek settlement. The only issue is that it is occupied by the Getae, and are not easily beaten.
He's well placed to create a Macedonian Empire in OTL ERE. But this is optimistic. BUT! Alexander The Great may be known as a greater ruler than conqueror, as he isn't going to die of malaria exceptionally young, and may well be able to establish a strong Empire.
Would he want to crush Persia in his older age? Perhaps, and with a united Empire, and his talents? It'd be very possible.
However, Alexandria on the Bosphoros (OTL Constantinople) may be the most important city in his Empire, followed by Alexandria on the Nile.