The 49ers take their high-powered offense south of the border to square off with their NFC West division-rival Cardinals. San Francisco is a sizable favorite and should handle their business. Thus, they’re the more well-represented club. However, gamers will need to fade some of San Francisco’s talented skill-position players and use at least one player from the Cardinals. The following analysis will help whittle the player pool to a manageable size.

Game: San Francisco 49ers at Arizona Cardinals

Spread: SF -10.0 Points

Over/Under: 43.0 Points

49ers Analysis: The 49ers are a run-first team. It's in their DNA. According to numberFire, in the last two games, with Christian McCaffrey up to speed, they ran 49 times with non-quarterbacks and passed 47 times in neutral game scripts.

CMC's snap share dipped from 81% in Week 8 to 65% in Elijah Mitchell's return in Week 10. Still, San Francisco's prized trade acquisition was busy last week. CMC had 14 carries for 38 rushing yards, one touchdown, four targets and 39 receiving yards.

Meanwhile, Mitchell was explosive as his running complement, rushing 18 times for 89 yards. Fortunately, the matchup is decent for both backs. According to Football Outsiders, the Cardinals are 16th in rush defense Defense-Adjusted Value Over Average (DVOA). Further, per Pro-Football-Reference, running backs have averaged 124.0 scrimmage yards and 4.6 receptions per game, averaged 4.52 yards per carry and scored 11 touchdowns. And, of course, the matchup should be good for the 49ers since they're more than a touchdown favorite.

Jimmy Garoppolo has averaged 259.3 passing yards per game, thrown for four touchdowns and one interception and rushed for one touchdown in his last three games. He's used his bevy of weapons to play efficiently and is a worthwhile choice in a good matchup against Arizona's below-average pass defense, which is 19th in pass defense DVOA.

The matchup is mouthwatering for one of San Francisco's top-shelf pass-catchers. According to Football Outsiders, tight ends flame the Cardinals for the most receiving yards per game (73.6). The runway is clear for George Kittle to dominate tonight.

San Francisco's No. 3 wideout, Jauan Jennings, also has a tasty matchup. Other wideouts (wide receivers not deemed the No. 1 wide receiver or No. 2 wide receiver by Football Outsiders) have averaged the third-most receiving yards per game (53.7) against the Cardinals.

The third-year wideout isn't a threat to overtake Deebo Samuel or Brandon Aiyuk on the depth chart, but he has earned targets when on the field. According to Pro Football Focus (PFF), Jennings was targeted on 22.2% of his 18 routes last week, securing all four for 40 yards. Jennings has been targeted on 20.4% of his routes and earned multiple targets in every game he's played this year. Further, he has had multiple receptions in his previous five games.

Cardinals Analysis: Colt McCoy had a rock-solid game in Kyler Murray's stead last week, but his fantasy numbers weren't exciting. Further, the matchup is challenging. The 49ers are 10th in pass defense DVOA.

Arizona will likely air it out regularly with either quarterback under center, though. McCoy attempted 33 passes, and James Conner handled all 16 of Arizona's non-quarterback carries in a neutral game script last week. Moreover, the Cardinals have attempted 149 passes, and just 88 rushes by non-quarterbacks in neutral game scripts in Murray's starts this season. And Arizona's probable negative game script will force them to throw.

DeAndre Hopkins and Rondale Moore are the most exciting pass-catching options on the Cardinals. The duo was targeted at a high rate last week when McCoy started. Nuk had a 37.8% Target Share, 10 receptions and 98 yards last week. The second-year wideout was also fed the rock, owning a 35.1% Target Share in Week 10 and reeling in nine receptions for 94 yards.

Hopkins was also cruising in three games with Murray this year. In those contests, Nuk had 26 receptions, 298 receiving yards, and two touchdowns. Moore also chipped in, securing 16 receptions for 192 yards and a touchdown. Therefore, Nuk and Moore can get the job done tonight.

Maxx Williams is a dark horse punt and a sneaky pivot from chalk-trap Trey McBride. Tight ends have found the sledding tough against the 49ers this year, averaging the fifth-fewest yards per game (36.4) against them. The matchup is suboptimal for Williams and McBride.

Yet, Williams is still intriguing since he's flashed some potential in the NFL and will be overlooked. Eating chalk when it's a rookie who's yet to flash and has a nightmare matchup is a recipe for disappointment.

Final Thoughts: CMC is my favorite choice for the captain/MVP spot. Finally, gamers should build 49er-heavy lineups, including some five-to-one builds at DraftKings.

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Josh Shepardson is a featured writer at FantasyPros. For more from Josh, check out his archive and follow him @BChad50.