The Amhara ethnic group traditionally ruled the country and is likely to lobby for one of their ruling party members to take over.
The death of the strongman raises questions about Ethiopia's influence over other neighbors. Adekeye Adebajo, executive director of the Centre for Conflict Resolution in South Africa, said:
"If a new government decides it has to focus internally, that could affect what happens in the region. If there is a weaker, less confident leader, it may mean Ethiopia is not so confident in playing that foreign policy role. That could have a direct impact on security in the Horn of Africa."
Domestic instability was "absolutely" possible, Adebajo said. "Meles's deputy is seen as quite competent and substantial but nobody has the same clout to keep the complicated coalition together.
Meles has always been seen as one of the most thoughtful leaders we produced as a continent. There will be a vacuum. They're in uncharted waters and it will take a while before we see what emerges."
Meles built one of the strongest armies on the continent, and it saw action in Somalia and Sudan with mixed results. In 1998 he went to war against neighboring Eritrea, costing tens of thousands of lives, and his demise creates fresh uncertainty among the sworn enemies.
When the Ethiopian military wanted to march all the way to the Eritrean capital, it was Meles who stopped them, Dowden said. "There was a crucial moment when Meles sacked hundreds of officers because they didn't like the settlement with Eritrea. I wonder now whether that might bubble up again, because it's never been settled."