The Spaniard managed Tottenham between 2007 and 2008, leading them to a League Cup title before being sacked with the London club rock-bottom of the Premier League.
Ramos is now in charge at Ukrainian side Dnipro and will hope to exact a measure of revenge on the club who dismissed him after less than a year at the helm.
Dnipro, who have not played a competitive game since December because of the mid-season break in the Ukraine, are enjoying a strong season in both domestic and European competition, sitting fourth in the domestic table and having qualified for the knockout stages of the Europa League after finishing second behind Fiorentina in Group E.
However, it is Tottenham who are likely to approach the first competitive meeting between the two sides as favourites following a resurgence under new coach Tim Sherwood.
Tottenham have lost just three of the 12 games since the dismissal of Andre Villas-Boas in December, with Sherwood reinvigorating a side whose hopes of reaching next season's Champions League had looked to be fading.
The London club are only three points behind Liverpool in the race for fourth place in the Premier League, but they will now switch focus to the Europa League as they seek to add the title to the two UEFA Cup crowns already on the club's honours list.
And, although Tottenham visit Norwich City in the league on Sunday, Sherwood insists that the club have the resources to cope with the fixture congestion.
"I love it (the Europa League)," Sherwood said. "There are a lot of games coming up but we haven't got to worry about that.
"We're out of the rest of the competitions and we've got a big enough squad here to cope.
"There will be opportunities for other people to play because the games will come thick and fast and you're playing on Thursday and Sunday."
Tottenham still have a number of injury concerns going into the game, with midfielders Sandro (calf) and Gylfi Sigurdsson (thigh) both doubts.
Forward Erik Lamela (thigh) remains on the sidelines, along with defender Vlad Chiriches (back).
Dnipro, meanwhile, will look to the likes of winger Yevhen Konoplyanka – the subject of a failed approach from Liverpool in January – and strikers Roman Zozulya and Yevhen Seleznyov to help guide them to a shock triumph.
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