Heaton has been ruled out for the rest of the season due to "significant knee ligament damage" picked up in Wednesday's 2-1 win at Burnley.
The goalkeeper joins Wesley on the sidelines for the remainder of the campaign, with the Brazilian also suffering a serious knee injury in the victory at Turf Moor.
Both were unlikely to feature at Craven Cottage, with Dean Smith preferring to use the cup competitions as a chance to play his fringe stars.
With Jed Steer also injured, Orjan Nyland is expected to come in between the sticks after his cameo on Lancashire, but it is unclear how those in front of him will line up.
Smith selected a back three for the victory against Burnley but, with numbers light in his squad, may revert to a four-man defence.
Tyrone Mings could be involved as he looks to build his fitness after returning from a hamstring injury on New Year's Day.
James Chester is likely to start in defence, with Ahmed El Mohamady another option at the back.
In Wesley's absence, Jonathan Kodjia should lead the line and will look to prove himself, with the Villans expected to sign a new striker this month following their recent injury blows.
While Villa sit 17th in the Premier League, Fulham are fifth in the second tier and aiming for an immediate return to the top flight.
Things have not been easy in recent weeks although they remain well in the hunt for promotion.
The Cottagers won the last time the pair met - in the Championship play-off final in May 2018 - and, having invested heavily that summer, the pair's approach to the top flight has a number of comparisons.
Scott Parker seems to have calmed things down after last term's sackings of Slavisa Jokanovic and Claudio Ranieri.
However, his team come into the game on the back of a 2-1 defeat to Reading.
Former regulars Marcus Bettinelli and Alfie Mawson were on the bench for that game and are likely to come into the XI although the latter may face a fitness test.
Ivan Cavaleiro could also start out wide in a re-shuffled frontline to afford Aleksandar Mitrovic a rare rest.
The man who scored the goal that separated the pair 19 months ago at Wembley, Tom Cairney, is a doubt.
Fulham have not made it past the third round of the FA Cup for two seasons.
However, that is better than Villa, who have fallen at the first hurdle in each of the last three years.