The last-place Rockies are showing few signs of being able to change that Wednesday night.
Cain looks to set a career high in wins by getting another against Colorado and move the San Francisco Giants closer to another NL West crown.
Cain (14-5, 2.93 ERA) is 6-1 with a 3.00 ERA in his last nine starts against the Rockies (58-89), and he's dominated them at home in five outings in that span - going 4-0 with a 1.69 ERA while San Francisco (85-63) has won all five.
The right-hander beat them there most recently Aug. 11, yielding two runs and seven hits in 7 1-3 innings of a 9-3 victory.
The three-time Al-Star seems likely to extend his streak with the Rockies having lost four straight and 11 of 13.
The Giants added to Colorado's woes Tuesday, beating the division rival 6-3 and have won the first two of this four-game set.
They're 8 1/2 games ahead of second-place Los Angeles in the West race with 14 games to play, well on their way to a second division title in three years.
Cain is 4-0 with a 2.68 ERA in seven starts, battling Arizona to a 6-2 win Friday. He allowed one run and four hits with five walks while tossing 106 pitches in five innings.
''That was a gutsy effort," manager Bruce Bochy said. "It just got to a point where I had to go get him."
Marco Scutaro continues to be a force at the plate for the Giants, hitting .355 with 32 RBIs since being acquired in a deal with Colorado on July 27.
The second baseman has a .486 average in eight games, and that includes going 12 for 23 in five meetings with his former team after pounding out five hits so far in this series.
Angel Pagan is also on a tear, batting .336 with 11 doubles, seven triples and 28 runs in 30 games. He's managed at least one hit in 25 of those contests, including his RBI triple Tuesday.
As a whole, the Giants are finding plenty of success with the bats versus Colorado, hitting .315 while leading the season series 12-4.
The Rockies have dropped nine of 10 on the road, but are expected to welcome Carlos Gonzalez back from left hamstring tightness.
He was a late scratch Tuesday after appearing as a pinch-hitter in the series opener.
Gonzalez leads Colorado with a .307 average and 85 RBIs, while his 22 homers and second to Wilin Rosario's 25.
Rosario latest homer Tuesday tied the Rockies' rookie record set by Todd Helton in 1998. Rosario is 9 for 27 with two homers and seven RBIs in seven games.
''It's pretty impressive. I'm pretty happy about it,'' he said. ''It's tough being a catcher. This is my first year of playing a lot and the game is quicker up here.''
Tyler Chatwood (4-4, 5.65) is expected to get the ball, and he's 0-1 with an 8.49 ERA in three starts with all of them coming on the road.
The right-hander has failed to complete at least four innings in two of those outings, including Friday's 7-4 defeat at San Diego. He didn't get a decision while surrendering four runs and five hits in 3 2-3 frames.
Chatwood is 1-1 with a 1.59 ERA and one save in three games - two starts - against the Giants. He beat them in his only appearance in San Francisco on Aug. 10, yielding three hits in five innings of a 3-0 victory.
He's had success against Scutaro and Pagan, holding them hitless in five at-bats each.