The San Francisco Giants' recent success on the road has aided their quest for a second NL West title in three seasons.
San Francisco (75-58) has won 18 of 24 on the road following a 5-2 victory over Chicago on Saturday, and former Cub Xavier Nady played a big role in his Giants debut.
Nady, called up from the minors when the major league rosters expanded for September, hit a three-run double in the first inning.
"Without question, he can help us. He can help us out in left field, and he's going to get some playing time," manager Bruce Bochy said. "He'll be out there tomorrow."
Cain (13-5, 2.82 ERA) will try to deliver another victory while matching his single-season career high. The right-hander had 14 wins in 2009.
He's 3-0 with a 1.82 ERA over his past four starts - the last three on the road - but needed two ninth-inning runs from his teammates to avoid a loss in Houston on Tuesday. Cain allowed two runs, six hits and three walks over 7 1-3 innings during that 3-2 victory.
"Those guys have done a great job for me all year, picking me up at times and making some spectacular plays behind me," Cain said. "As a pitcher that just motivates you to keep wanting to go out there and pitch well."
Cain has performed extremely well in his last eight matchups against the Cubs (51-81), going 4-0 with a 0.79 ERA. He beat them on June 2 in San Francisco, giving up one run over eight innings and striking out seven in a 2-1 win.
The right-hander has tossed 20 consecutive scoreless innings at Wrigley Field, allowing nine hits in three starts but not earning a win in any of them.
Cain now faces a Chicago team which has scored the second-fewest runs in baseball and has lost 23 of 31.
The Cubs counter with Travis Wood (4-11, 4.71), who is 0-8 with a 6.66 ERA in nine starts since the All-Star break.
The left-hander, though, has given up three runs or fewer in five of his last six outings, including a 4-1 home loss to Milwaukee on Tuesday.
Wood gave up three runs over seven innings in his second loss to the Brewers in as many starts. He also provided the only run on his third career homer.
"It's a moot point when you still lose the ballgame," he said.
Wood is 0-2 with a 4.74 ERA over three career starts against the Giants but has yielded a combined three runs in the last two. He allowed one run over seven innings and struck out seven in a 2-0 loss at San Francisco on June 3.
Nady is 4 for 8 with two doubles in his career against Wood, and Hunter Pence is 5 for 12 with a triple and a home run.
Buster Posey is 5 for 7 in this series and a career .440 hitter at Wrigley.