Bosnia-Herzegovina's World Cup hopes have been dealt a cruel blow with key midfielder Zvjezdan Misimovic ruled out of the return leg qualifier against Portugal.

Bosnia finds themselves a goal to the negative after Portugal won their home leg 1-0 and go into the match as favourites as Bosnians will be without Misimovic and two suspended players.

But despite their supposed shortcomings, Bosnia coach Miroslav Blazevic is confident his spirited charges can overcome adversity and push past the Portuguese at Zenica's Bilino Polje stadium.

"Misimovic is unfit to play on Wednesday. He received a knock in the first leg in Lisbon and Medunjanin will replace him," Blazevic told a news conference on Tuesday.

"I can guarantee that we will play our hearts out to accomplish what might seem like an impossible mission. It wouldn't be the first time that a more determined team got the better of a more heralded one."