Urena, Miami's Opening Day starter the past two years, is 0-0 but with a 0.84 ERA in 10 2/3 career innings against the cross-state Rays.
Tampa Bay, which blanked the host Marlins 4-0 on Tuesday to open the brief two-game series, will counter Urena with opener Ryne Stanek (0-1, 2.57 ERA). It will be Stanek's 17th appearance this year, including 11 starts.
The Rays hope to get more performances on Wednesday like the one they received Tuesday from right fielder Avisail Garcia, who went 3-for-4 with three RBIs. He launched a 471-foot homer -- the longest blast by a rival player ever at Marlins Park -- and added a pair of RBI singles.
"I was shocked how far that ball went," Rays manager Kevin Cash said of Garcia's homer. "I know they had a guy here for many years in (Giancarlo) Stanton who hit balls a long way. But that's got to be right up there with some of his majestic shots.
"It just kept going up. To get it up over the batter's eye is pretty impressive."
Meanwhile, poor run support has long been a factor for Urena, who made his major-league debut in 2015. At Marlins Park, he has a horrible 11-26 record but an ERA that isn't nearly that bad at 4.20.
Overall this season, Urena is 1-5 with a 4.82 ERA. But he has quality starts in four of his past five outings, and he has lasted at least six innings in five straight appearances.
For all of Miami's issues this season, the Marlins have used the same five starting pitchers all year. The only other teams who can lay the same claim are the Cincinnati Reds and the Washington Nationals.
Urena will have to be careful early as the Rays tend to ambush teams. Entering this week, the Rays ranked second in the majors in first-inning scoring, outscoring opponents 32-14 in that frame.
Meanwhile, in Tampa Bay's system, Stanek is used as an "opener" and has not pitched more than two innings in any appearance this season. Still, he is part of a Rays pitching staff that started this week leading the majors in ERA (2.96). Rays starting pitchers were also atop the majors with a 2.52 ERA.
In four career games and innings against the Marlins, Stanek is 0-1 with a 2.25 ERA. In two games and innings at Marlins Park, he is 0-1 with a 4.50 ERA.
Cash was asked about his team's focus for Wednesday's game given that Tampa Bay will visit its division rival, the New York Yankees, this weekend.
"I certainly hope we are not overlooking this series (against Miami)," Cash said. "We have not played very well against (Miami) the past couple of years, whether in our ballpark or theirs. (The Marlins) are young. They play hard. We have our work cut out."
Meanwhile, the Marlins -- in last place in the National League East -- are just hoping to compete.
"I don't feel uncomfortable at all with our effort," Marlins manager Don Mattingly said. "I think the guys have been working. The attitude's been good. We haven't put enough runs on the board to be consistent.
"There's always a light at the end of the tunnel. We know it's there. Sometimes you can't see it. But you've got to know it's there, and that's the point for us as a staff."