Paraguay drew with Italy in their opening World Cup match and now sit on top of the group with four points, with world champions on two points after a surprise 1-1 draw with New Zealand on Sunday.
Paraguay's final match is against New Zealand on June 24 while Italy will take on Slovakia.
"It is not only about qualifying. We want to finish first. We've been given a realistic chance now to go into the last game and win the group," Santa Cruz told reporters after the match.
"Paraguay have never been to the quarter-finals in their history. We know the goal we have set for ourselves but once we get there we want to keep getting better."
The winners of Group F will meet the runners-up of Group E in the last 16, while the second-placed team will meet the Group E winners. The Netherlands currently top Group E.
"Of course you think about possibilities. We know that once we qualify we could play against Holland," Santa Cruz said.
"The main thing is to qualify, now we have the chance in the last game to think we can finish first in the group."
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