That would make no sense to abandon the Andromeda galaxy after ONE game. They would be be nutty than squirrel poo.
This game takes place in the Helius cluster of Andromeda. If I were to guess, the story will probably involve a local threat and at the end awakening a greater threat of the Remnant while also discovering a greater truth. That truth, I imagine, will be that Andromeda has a relay network or something equivalent, and that the Remnant prevented the Reapers from continuing the harvest there.
Then, I imagine, subsequent game(s) would involve exploring the greater galaxy of Andromeda, an amplification of the Remnant threat level, and an eventual realization that the threat now also involves the Milky Way.
Enter a likely return to the Milky Way.
That's the most predictable over arching story I can think of - it will likely be some semblance or variant of it, with the general theme of "some great threat is discovered, threat now impacts Milky Way, ME3 endings are rendered irrelevant".