Condominas stated "There is one thing we are absolutely sure of - there will be no more Shepard, and the trilogy is over.
But what might Mass Effect 4 look like? Bioware's producer shared the most faint of outlines for the universe:
"So first, we don't want to make 'Shepard 2′, or Mass Effect 4 with like, 'oh there's no more Shepard but you're a soldier in the universe'. So this will be a very, very different context for sure, and nothing has been decided on the rest.
This is really our starting point. Now the Mass Effect universe is vast, and very, very rich. So at this point in time, we don't even know what kind of time frame we're going to be in. All we're doing is more gathering ideas from the teams, gathering feedback to see several things."
It's gonna be very tough to follow up with a story that is as engrossing as Sheppard's Mass Effect arc - I do hope that ME4 is set well after the events of ME3 and is not a prequel - I'm wary of prequels for video games....