The Bluebirds sacked Neil Harris and turned to Barnsley-born coach McCarthy after a six-game losing run that leaves the club 13 points off the playoffs.
Barnsley have a more realistic chance of breaking into the top six as they are five points better off than City heading into this midweek clash, despite a bad run of their own.
A 1-0 home loss to Queens Park Rangers proved to be the final game in charge for Harris, who struggled to build on last term's fifth-place finish in his second season in charge.
McCarthy's appointment may not have been universally welcomed by City supporters, but it is only a short-term arrangement until the end of the campaign.
That is unless the former Ipswich Town, Wolverhampton Wanderers and Sunderland boss can guide Cardiff up the division and back into top-six contention.
That is a major task but one McCarthy, no stranger to life in the Championship, is relishing. If City are to have any hope of earning promotion, though, they need to start getting wins on the board.
The Welsh side have lost five in a row in the league and, on current form, will be more concerned about a relegation scrap than competing for a place in the Premier League.
Coincidentally, McCarthy's most recent Championship match was against Barnsley in April 2018 when picking up a 1-0 win as Ipswich Town boss.
Whereas Cardiff have had a week to prepare for this match, Barnsley were in FA Cup action at the weekend, overcoming fellow second-tier side Norwich City 1-0 to set up a last-16 tie with Chelsea.
In the league, though, they have lost three in a row without scoring, most recently losing 1-0 at Watford.
The Yorkshire side also have a poor record against Cardiff, with their 3-0 reverse in South Wales earlier in the season making it five defeats in a row in this fixture.
Still, Valerien Ismael will know that a victory on Wednesday could potentially propel his side within two spots of the playoffs with some winnable fixtures ahead.
Barnsley Championship form: LWWLLL
Barnsley form (all competitions): WLWLLW
Cardiff City Championship form: WLLLLL
Cardiff City form (all competitions): LLLLLL
McCarthy will no doubt want to put his own mark on this City side, which could mean a few changes on Wednesday night.
Cardiff striker Moore, who netted 21 goals in 51 league appearances for Barnsley between 2017 and 2019, has never scored against the Tykes in the EFL in six previous appearances.
Carlton Morris has impressed in his first couple of outings for the club and is pushing for a place in the starting lineup.
Cauley Woodrow had eight goals in 21 league appearances this term and is expected to lead the line for Ismael's men.
Barnsley possible starting lineup:
Walton; Sollbauer, Helik, Andersen; Brittain, Mowatt, Kane, Styles; Adeboyejo, Woodrow, Chaplin
Cardiff City possible starting lineup:
Smithies; Ng, Morrison, Nelson, Bennett; Wilson, Vaulks, Ralls, Ojo; Watters, Moore
We say: Barnsley 1-1 Cardiff City
Barnsley have lost three league games in a row, though they earned a morale-boosting cup victory in midweek and will be up for this game against McCarthy's Cardiff.
The Bluebirds quite simply need to string together wins if they are to climb the division, and we can see them at least ending their losing run at Oakwell on Wednesday.
Top betting tip
body check tags ::