England were 46 for two wickets against Pakistan at the close of the fourth day in Sharjah on Wednesday, chasing a target of 284 to win the third and final Test and draw the series.
Captain Alastair Cook was 17 not out with Joe Root on six after Moeen Ali and Ian Bell were dismissed by Shoaib Malik in the space of two overs.
Having taken a first innings lead of 72, England finally dismissed Pakistan for 355 in their second innings, with opener Mohammad Hafeez making 151.
Pakistan, who have never lost a series in the United Arab Emirates since their home matches were moved there in 2010, won the second Test by 178 runs after the first was drawn.
They struck two heavy blows in the last session when Malik, playing in his last Test, dismissed Moeen Ali and then Bell in quick succession with the score on 34.
Moeen, who has been unable to make a success of his role as opening bat, fell leg before for 22 and Bell lost his off stump without scoring.
Root, who survived a controversial leg-before decision as Pakistan used up their final DRS review, stayed in until the close along with Cook, and at least one of them must make a big total if England are to score the 238 runs still needed.
Earlier, Hafeez (151) struck his ninth Test century to help Pakistan consolidate their position after losing nightwatchman Rahat Ali for a duck.
England challenged the umpire's not out verdict against Hafeez on the first ball of the day off leg-spinner Adil Rashid but could not get it overturned.
Wicketkeeper Jonny Bairstow missed a stumping chance in the same over and later Stuart Broad dropped a tough return catch from him.
Skipper Misbah-ul-Haq shared a fifth-wicket stand of 93 with Hafeez and when Malik grabbed his two wickets Pakistan became firm favourites to win the series if not the match as well.
"We're very happy with the total on the board and we're very confident of winning the game," Hafeez told Sky Sports.
