NFL DFS picks, Thursday Night Football: 49ers vs. Rams daily fantasy strategy, advice for DraftKings, FanDuel

The Week 5 NFL schedule opens with a NFC West rivalry game with the Los Angeles Rams set to host the San Francisco 49ers on ‘Thursday Night Football.’ Kickoff is scheduled for 8:15 p.m. ET at SoFi Stadium and the over/under is 46.5 points. The game features a loaded NFL DFS player pool, with some of the biggest names in the sport like Christian McCaffrey, Matthew Stafford, Puka Nacua, and Kyren Willias leading the way. George Kittle (hamstring), Brandon Aiyuk (knee) and Brock Purdy (toe) are among the players out for the Niners.

Finding undervalued players at a cheap price is still the key to building a winning NFL DFS strategy in Showdown contests — especially with this matchup featuring so many big-name players. Should you target potential DFS values like Davante Adams, or Blake Corum to pair with the bigger-name players for Thursday Night Football DFS lineups and NFL DFS stacks? Before making any NFL DFS picks for Rams vs. 49ers on Thursday Night Football on sites like DraftKings and FanDuel, be sure to check out the NFL DFS lineup advice, strategy and player stacks from SportsLine NFL daily Fantasy expert Jimmie Kaylor. 

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Kaylor is a NFL betting and DFS expert for SportsLine, who opened the 2022 NFL season by winning DraftKings’ NFL Showdown Thursday Kickoff Millionaire contest. He edged out over 355,000 other entrants in the contest and also has multiple five-figure tournament wins on his DFS resume. Kaylor has covered the NFL and college football for close to a decade as a member of the Pro Football Writers of America, and his background as a former college and NFL player gives him a unique perspective when building his fantasy lineups and locking in his betting picks. 

Now, Kaylor has turned his attention to the Thursday Night Football matchup of 49ers vs. Rams and just locked in his top daily Fantasy football picks. You can only see his Thursday Night Football DFS picks and analysis at SportsLine.

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Top NFL DFS picks, lineups, stacks for Rams vs. 49ers

One of Kaylor’s top DFS picks for Thursday Night Football is 49ers running back Christian McCaffrey. The former Stanford standout had his 2024 campaign derailed by injury, limiting him to just four games. In that span, he carried the ball 50 times for 202 yards (4.0 yds per carry) and added 15 receptions for 146 yards, but failed to find the end zone. 

In 2025, through three games, he’s logged 52 carries for 176 rushing yards and caught 25 passes for 213 yards and a receiving touchdown, continuing to serve as a dual threat in the 49ers’ offense. Over his career, McCaffrey has amassed more than 6,500 rushing yards and over 4,600 receiving yards, and he’s earned multiple Pro Bowl nods and an NFL Offensive Player of the Year award in 2023. See who else to roster right here.

Part of Kaylor’s optimal NFL DFS strategy also includes rostering Rams wide receiver Puka Nacua. The former fifth-round pick out of BYU followed up his breakout rookie season with a solid 2024 campaign, catching 79 passes for 990 yards (12.5 yards per catch) and tallying three touchdowns over 11 games. He has since solidified his place among the top wide receivers in the NFL today.

In 2025, through three games, he’s been even more productive, hauling in 29 receptions for 333 yards and adding a rushing attempt for 52 yards. From a career standpoint, Nacua has already earned recognition with Second-team All-Pro and Pro Bowl honors in 2023, and holds rookie receiving records such as the most receiving yards in a rookie season. In Week 4, Nacua erupted with 13 catches for 170 yards and a score in the Rams’ 27-20 win over the Indianapolis Colts. You can see the rest of Kaylor’s NFL DFS picks here.

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How to build NFL DFS lineups and stacks for 49ers vs. Rams

Kaylor is also targeting another undervalued player who could explode for huge numbers on Thursday Night Football. This pick could be the difference between winning your tournaments and cash games or going home with nothing. You can only see who it is, and get the rest of Kaylor’s NFL DFS picks, at SportsLine. 

So who is Jimmie Kaylor including in his optimal NFL DFS lineups for 49ers vs. Rams on Thursday Night Football, and which under-the-radar NFL DFS picks offer huge value? Visit SportsLine now to see optimal NFL DFS picks, rankings, advice, and stacks, all from SportsLine’s proven DFS expert who won a single-game millionaire maker tournament, and find out.