The midfielder is reportedly set to undergo surgery on a problematic ankle during the off-season in a bid to make a timely recovery before the commencement of the 2019-20 Italian Serie A season.
The news is a massive blow to Ghana, whose squad have already been disrupted by injuries and controversies.
Udinese centre-back Nicholas Opoku is also unlikely to make the travelling party as he is currently still out injured.
USA-based Harrison Afful is just about resuming training, having been out of action since suffering a jaw fracture while in action for club side Columbus Crew.
On Monday, captain Asamoah Gyan announced a sensational retirement from international football after being asked to relinquish the armband to deputy Andre Ayew for the June 21-July 19 Cup of Nations.
Ghana, whose provisional squad is expected to be announced soon, have been drawn against defending champions Cameroon, Benin and Guinea-Bissau in Group F of the continental showpiece.