The USA will come up against powerhouse nations Germany and Portugal, as well as Ghana, in Group G at the showpiece event in Brazil.
But Republic of Ireland and LA Galaxy captain Keane has painted a bleak picture for Jurgen Klinsmann's men at the upcoming World Cup.
Speaking to TMZ Sports, the 131-cap international veteran said not even Argentina star Messi could help the USA progress to the knockout round.
"I'll be honest with you, I don't care if they had Messi, with the group they have they're going to struggle," said Keane, whose only appearance at a World Cup came in 2002, when he scored three goals in four games in South Korea and Japan.
"It's going to be quite tough with the teams that are in there."
The USA will be without Landon Donovan for the World Cup after Klinsmann controversially overlooked the nation's all-time leading scorer.
Donovan had made the initial squad but there was no room for the 157-cap veteran in USA's final 23-man roster.
Keane said he could understand his Galaxy team-mate's frustrations after missing out on a fourth World cup appearance.
"I'd be pissed off," the 33-year-old said."It's a bit of a shock to everybody.
"He (Donovan) is one of the best players in the MLS and he has shown that for many years. But sometimes you have to respect the manager's decision.
"He has done what he has had to do for the national team over the years but he should be brought because he is one of their best players."
