The first leg finished 1-1 in Madrid and Barca's dominance of all things domestic this season makes them favourite to advance on home soil.
But Fabregas reckons his side have already missed one chance to deliver a killer blow to Jose Mourinho's side and they cannot afford to do so again.
"We had our chances to make it 2-0 in Madrid," he told Barcelona's website. "In the return leg we will need to be as effective as possible, because they are very effective. We have to be on target in front of goal if we want to get to the final."
Barcelona are chasing a treble with the Primera Division title all but sewn up, although their Champions League hopes are dangling by a thread after a surprise 2-0 loss away to AC Milan in the first leg of their tie.
For Madrid, the cups have even more currency as their only hopes of silverware in a season where they have fallen drastically short of expected standards in the league.
Mourinho's side trail Barca by 16 points in the league but can salvage some pride with cup success.
With all the attention a Clasico fixture attracts, it would be easy to forget it is one of two semi-final second legs this week with Atletico Madrid and Sevilla ready to settle their tie, in which Atletico will head south with a 2-1 lead.
Atletico's 1-0 victory over Espanyol yesterday preserved their 100 per cent home record in the league this season and restored their four-point advantage over city rivals Real.
But while second place in the league is their clear priority, their success in that arena is giving the players plenty of confidence to pursue a cup trophy.
"We're really looking forward to the match," Juanfran said. "The tie is very close and very open. We are thinking of going there and beating Sevilla. We
have to win at the Sanchez Pizjuan.
"We have won at difficult grounds. Atletico Madrid can win in any stadium and Sevilla is no exception. Let's go there with high spirits."
League form makes Sevilla the clear underdogs on Wednesday not only in this tie but in the competition at this stage, as La Liga's top three are joined by the side sitting 12th.
But the away goal in Madrid gives them clear cause for hope and they are taking encouragement from an impressive display - even in defeat - as they lost 2-1 at Barcelona on Saturday evening.
"We are a bit disappointed but also reassured," forward Manu del Moral said. "It is a difficult place to play and we need to keep the same dynamic on Wednesday.
"This gives us confidence for the cup and in that respect we are reassured."