The game is booked to occur on the few days of 16 and 17 April.
Notwithstanding, designing works mean no trains are running from one or the other city to or from London from 15 to 18 April.
Andy Burnham, the city chairman of More noteworthy Manchester, and Liverpool chairman Steve Rotheram both say the game should be at a "more available arena".
In a joint letter to the Football Affiliation, Mr Burnham and Mr Rotheram said: "Without fast, direct trains, many individuals will be left with no choice except for to drive, fly, make excessively complex rail excursions or book for the time being convenience.
"Whenever you factor in the increasing expenses of fuel, obviously allies of the two clubs going to this game will confront unnecessary expense and bother - and that is before any ecological effect is thought of.
"There are additionally critical strategic and wellbeing contemplations. With great many fans making the long excursion south, there will be enormous numbers merging on the M6, which is probably going to be extended to limit by bank occasion traffic.
"A solitary mishap would gamble with the whole motorway being brought to a stop and fans missing the start up."
The pair said they comprehended the designing works had "been booked starting around 2019 and that the FA was intelligibly made mindful of them last pre-winter".
They added: "Throughout the last year, we have heard the motto 'football without fans isn't anything' ordinarily. Assuming this choice is passed on to stand, and individuals are either valued out of this game or unfit to go to for different reasons, those words will be good for nothing to many.
"We accept the clearest arrangement is to move the game to a more available arena and propose to work usefully with you to get that going."
Before the letter, the FA said it was liaising with the two clubs and working with Organization Rail and Public Express to track down an answer "so allies of the two groups can go to and from the apparatus with as insignificant disturbance as could really be expected".
The other FA Cup semi-last is between London clubs Chelsea and Gem Royal residence so there is no issue over the setting.
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