The Millers have lost back-to-back games without scoring to remain 22nd, while Boro are officially out of the playoff race after also losing successive matches.
Thanks to a number of games in hand owing to a coronavirus outbreak in their camp earlier this year, Rotherham have long been in control of their own survival destiny.
However, successive 1-0 losses to fellow strugglers Coventry City and Birmingham City has left United four points from safety with two games in hand on 21st-placed Derby County.
Paul Warne's men need to get a win on the board on Wednesday evening, then, especially with high-flying Barnsley and Brentford to come in their following two games.
That could prove tricky, though, as they have lost five of their last seven midweek league matches, most recently tasting defeat to Coventry last Thursday.
Middlesbrough make the trip to the New York Stadium with little to play for on the face of it as they are now mathematically unable to finish in the top six.
Neil Warnock had been flirting with the idea of another promotion just a month or so ago, but Boro have been badly out of form since the middle of March.
The Smoggies have lost four and drawn one of their last five games, with only Bristol City in worse form in the second tier over that period of time.
Indeed, Boro are looking to avoid losing three Championship games in a row for the first time in 14 months.
Rotherham were 3-0 winners when the sides met at the Riverside Stadium in January, meanwhile, and could win back-to-back games against Boro for only the second time ever.
Warne will surely be tempted to change his side on the back of successive matches without scoring, possibly meaning a return to the lineup for Ryan Giles.
Joe Mattock is the home side's only injury absentee, the versatile left-sided player having not played since before Christmas.
Warnock used a 3-4-1-2 at the weekend and, if that is again the case here, Marvin Johnson will be pushing for inclusion in the backline.
Rotherham United possible starting lineup:
Johansson; Ihiekwe, MacDonald, Wood; Harding, Wiles, Wings, Crooks, Giles; Smith, Ladapo
Middlesbrough possible starting lineup:
Bettinelli; Fisher, Hall, McNair; Spence, Howson, Saville, Johnson; Kebano, Bolasie; Akpom
We say: Rotherham United 1-1 Middlesbrough
Both teams are out of form, but there is no doubt that Rotherham have far more riding on this match than Boro, who are now jostling for position in upper-mid-table.
Boro boss Warnock has lost just one of his 18 managerial games against United - albeit that loss coming earlier this year - and we can see the visitors claiming at least a point.