A place in the last eight of the competition is at stake and Eusebio Di Francesco's men have it all to do if they are to progress, having suffered a 2-1 defeat in last month's first leg.
Roma are a 10/11 (1.91) shot with bet365 to qualify for the quarter finals for the first time in a decade; the Serie A side have yet to concede a home goal in the Champions League this term and they can be backed at just 8/13 (1.62) to win inside 90 minutes.
Shakhtar have suffered defeat in six of their last seven away matches in this competition; bet365 go 17/4 (5.25) that Paulo Fonseca's charges buck that trend by claiming a famous win in the Italian capital.
A draw, of course, would be enough to send the Ukrainian side into the last eight of the Champions League and bet365 go 3/1 (4.0) that the scores remain level at the end of 90 minutes.
Facundo Ferreyra was on target in the first leg of this tie and there seems little doubt that Fonseca's charges will again look to their talisman to make a mark in this match; the Argentine has scored 11 goals in his last 10 matches for his club.
Former Manchester City striker Edin Dzeko is expected to lead the line for the hosts and the Bosnia and Herzegovina captain will be desperate to add to his tally of three Champions League goals this season.
Roma to keep it tight
The Serie A side have kept a clean sheet in each of their three home matches in the Champions League thus far this term, while Shakhtar have failed to find the net in all but one of their last seven away matches in this competition; bet365 go 7/4 (2.75) that the hosts keep another clean sheet here.
Tips and predictions:
Given Shakhtar's wretched record on the road in the Champions League, bet365's 11/5 (3.20) quote for Roma to win to nil could represent good value for punters ahead of Tuesday's tussle.
Odds correct at time of writing. Please gamble responsibly.