Simoes is concerned that a group comprising current champions Atletico Madrid, Hapoel Tel Aviv and Pavel Vrba's Plzen, who competed in the Champions League group stages last season, could already be a lost cause for the plucky Portuguese outfit.
Before jetting off to Prague, Simoes told Jornal Record: "Our opponent is in the Czech First League.
"The Israeli opponents are top of their league and I remember them beating Benfica 3-0 in Tel Aviv.
"Atletico Madrid have won the Europa League twice in the last three years and beat Chelsea 4-1 recently, when it could have been six or seven.
"It's perhaps the toughest group that we could have ended up in after being in Pot Four.
"We're facing the top team from Pot One, the third-best team from Pot Two and the second-best team from Pot Three."
Academica returned to European competition after a 40-year absence by stunning Lisbon giants Sporting to win the Portuguese Cup at the end of last season - their first trophy since 1939.
And Simoes admits his team may have an outside chance of claiming victory in the Czech capital if they emulate that historic performance.
He added: "It's natural to be nervous.
"But we should treat the game as if it were a cup final, with a real sense of urgency."
Plzen have already played six qualifying games in order to reach this year's group stages, recording five victories and one defeat
Ominously for Academica, Vrba's men have won all three of their continental home fixtures without conceding.