The San Francisco 49ers will host the Los Angeles Rams in an NFC West rivalry matchup on Monday Night Football. The two teams will meet for the first time since last season's NFC Championship Game, which means plenty of tough decisions for your NFL DFS lineups. The NFL DFS player pool is loaded with star power like Cooper Kupp, Matthew Stafford, Deebo Samuel and George Kittle. Success in single-game slates while playing NFL DFS tournaments, cash games and 50-50s on FanDuel and DraftKings is all about identifying upside. Which players have the best NFL DFS matchups for Rams vs. 49ers and how should you differentiate your NFL DFS lineups? Before you make your NFL DFS picks for 49ers vs. Rams, be sure to see the NFL DFS advice, strategy and player projections from SportsLine daily Fantasy expert Mike McClure.

McClure is a legendary professional DFS player with over $2 million in career winnings. His methodology has led to enormous cashes on FanDuel and DraftKings. He took down two high-stakes tournaments on FanDuel in 2020 and recorded a pair of top-10 finishes in tournaments with over 130,000 entrants on DraftKings. His lineups also finished inside the top 1% in more than a dozen other tournaments. 

He uses a powerful prediction model that simulates every snap of NFL action, taking factors such as matchups, statistical trends and injuries into account. This allows him to find the best DFS values that he shares only with members at SportsLine.

In Week 3, McClure had Eagles quarterback Jalen Hurts as one of his core NFL DFS picks for both FanDuel and DraftKings: The result: Hurts had 340 passing yards, 20 rushing yards and three passing touchdowns, returning 30.6 points on DraftKings and 27.6 points on FanDuel. Anybody who had him in their lineups was well on the way to a huge day.

Now, McClure has turned his attention to Rams vs. 49ers and locked in his top daily Fantasy football picks. You can only see his picks and analysis at SportsLine.

Top NFL DFS picks for Rams vs. 49ers

One of McClure's top NFL DFS picks for Monday Night Football is 49ers wide receiver Brandon Aiyuk. After a strong rookie season, Aiyuk wasn't heavily involved in San Francisco's passing attack early in 2021, but he worked his way back into the coaching staff and Jimmy Garoppolo's good graces and finished the year with even better numbers than he'd had in 2020.

Aiyuk has played at least 88 percent of snaps in the last 14 games and has 57 catches for 872 yards and five touchdowns during that span. He's been targeted eight times in each of the last two games and has eight catches for 102 yards and a score in those contests despite the fact that the San Francisco offense hasn't reached 200 passing yards in a game this season. However, the Rams rank 23rd in the NFL in pass defense, so this could be a spot for Aiyuk and the 49ers' passing attack to spark their season.

McClure's optimal NFL DFS strategy also includes rostering Rams receiver Cooper Kupp. Coming off a season in which he caught 145 passes for 1,947 yards and 16 touchdowns, Kupp is once again putting up sensational numbers. He's caught 28 passes for 280 yards and three touchdowns and had a 20-yard rushing touchdown last week against the Cardinals.

Kupp has been targeted 35 times in the first three weeks of the season to lead the league and also has the highest target share (34.7 percent) and snap share (98.3 percent) of any NFL receiver. He had 11 catches for 142 yards and two touchdowns in the NFC title game win over San Francisco last season and has topped the 100-yard mark in his last three games against the 49ers. You can see the rest of McClure's NFL DFS advice here.

How to make NFL DFS lineups for 49ers vs. Rams

McClure is also targeting another undervalued option that could explode for huge numbers. 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 the rest of McClure's NFL DFS picks, at SportsLine

Who is Mike McClure including in his optimal NFL DFS lineups for Monday Night Football? And which under-the-radar player is a must-roster? Visit SportsLine now to see optimal NFL DFS picks, rankings, advice, and stacks, all from a DFS expert who has won millions with his daily Fantasy picks, and find out.