With qualification for the Europa League now unlikely, the teams, who are ninth and 10th respectively, are bidding to finish in the top half of the table.
While neither team have enjoyed the campaign which they would have hoped, there will be a strong desire to end an inconsistent season on a high.
Frankfurt, after agonisingly missing out on the Europa League final in 2018-19, have struggled since parting ways with key players during the summer transfer window, and only a resurgence since the resumption of action has helped their cause.
Losing 5-2 at Bayern Munich was the wake-up call which Adi Hutter's team required, and they have since gone on to record 10 points from a possible 15.
There will still be frustration that their one setback, after two wins on the bounce, came at home to struggling Mainz 05, but there was every indication at the weekend that the defeat was no more than a blip.
Facing a 1-0 deficit at half time, Frankfurt netted four times against Hertha Berlin after the break, which included two more goals for Andre Silva.
Six of the Portuguese's 10 strikes for the season have come since the restart, suggesting that Frankfurt would have been far higher in the standings had the AC Milan loanee found his touch earlier in the campaign.
From Schalke's perspective, David Wagner will be relieved that his side have recorded draws against Union Berlin and Bayer Leverkusen in their last two outings.
However, the Royal Blues remain without a win in any competition in 12 matches, a sequence which means that Wagner is under severe pressure to keep his job at the VELTINS-Arena.
Nevertheless, positives should be taken from holding Champions League-chasing Leverkusen, despite the equaliser for the visitors coming via a late own goal from Juan Miranda.
The point proved crucial in keeping the club above Frankfurt in the table and Wagner will hope that their recent improvement will ultimately pay off with a long-awaited win on Wednesday, something which has not been experienced since February 4.
Eintracht Frankfurt Bundesliga form: LDWWLW
Schalke 04 Bundesliga form: LLLLDD
Schalke will be without the versatile Daniel Caligiuri as the 32-year-old serves a one-match ban for five yellow cards.
Barcelona loanee Jean-Clair Todibo is expected to be available after recovering from an ankle injury.
Having started the last game among the replacements, Frankfurt forward Silva will almost certainly be handed a recall.
Hutter must decide whether to use Silva as a straight replacement for Bas Dost or combine the pair after their impressive showing against Hertha.
Eintracht Frankfurt possible starting lineup:
Trapp; Abraham, Hinteregger, Ndicka; Costa, Kohr, Rode, Kostic; Kamada; Dost, Silva
Schalke 04 possible starting lineup:
Nubel; Kenny, Oczipka, Kabak, Miranda; Boujellab, Schopf, McKennie, Bozdogan; Kutucu, Gregoritsch
We say: Eintracht Frankfurt 2-1 Schalke 04
Although Schalke have improved in recent games, we expect Frankfurt to inflict their first defeat in three outings on Wednesday. The home side remain as one of the form teams in the division, and they should have enough quality to ensure that they move ahead of their opponents in the table.