United's surprise 1-0 defeat by League One Leeds United in the FA Cup on Sunday left Alex Ferguson fuming and the manager will expect a backlash from his team against a City side yet to concede a goal under new manager Roberto Mancini.
Cash-rich City's priority is to break into the top four of the Premier League but with the scent of a first trophy since 1976 in their nostrils and the chance to inflict further pain on United, Wednesday's tie promises to be a full-bloodied affair.
"The fans are excited and so are the players," City keeper Shay Given told the club's website. "These should be two red-hot encounters."
United's defeat by Leeds was their first at home to third-tier opponents in the FA Cup for almost 80 years and was all the more galling for the fans as it was against a club with whom they have a bitter rivalry.
Ferguson, who had never tasted an FA Cup third-round defeat in more than 20 years at United, said he was "shocked and disappointed" by Sunday's result.
The Scot has used the League Cup to rotate his squad this season but the FA Cup setback means he will almost certainly resist any temptation to hold back some of his big guns for the second leg, especially with injuries stretching his defence.
"We'll make sure we're ready for Wednesday now," Ferguson said. "We had a team in mind but there will maybe be a few changes ... we have to get this result out of our system as quickly as possible."
City, who beat United at the same stage in the 1969-70 League Cup, will present a formidable challenge for the holders.
An outlay approaching 200 million pounds since the club was bought by Abu Dhabi billionaire Sheikh Mansour bin Zayed Al Nahyan has given the long-suffering fans genuine optimism they can, at long last, emerge from United's shadow.
A cup semi-final also gives Mancini the chance to finish off the job started by his predecessor Mark Hughes - sacked before Christmas after a run of two wins in 11 league games.
Former Inter Milan coach Mancini could not have dreamt of a better start to life in English club management.
Wins against Stoke City and Wolverhampton Wanderers left City fifth in the league before Saturday's 1-0 FA Cup triumph at Middlesbrough.
"We made a good start in the FA Cup at the weekend and we are close to a final in the League Cup," Given said.
"We have only lost twice all season so we are doing OK. One of those was against United and I have to admit it took a long while to get over that result."
City hope to have Brazil striker Robinho and defender Micah Richards fit but Shaun Wright-Phillips and Roque Santa Cruz are injury doubts and Stephen Ireland misses out.
Tuesday's semi-final between Blackburn Rovers and Aston Villa at Ewood Park will be the second meeting of the sides in three days after Villa knocked Rovers out of the FA Cup on Saturday.
