San Francisco 49ers at Los Angeles Rams Prediction & Betting Pick | NFL Week 5 Thursday Night Football

📅 Date: Thursday, October 1, 2025
🕖 Time: 8:15 PM EST
🏟️ Venue: SoFi Stadium – Inglewood, CA

The Week 5 edition of Thursday Night Football gives us a classic NFC West showdown between the San Francisco 49ers and Los Angeles Rams. Both teams enter at 3-1, but the momentum feels entirely different. The Rams are fresh off a thrilling road win against the Colts, while San Francisco dropped its first game of the year, falling to Jacksonville after costly turnovers.

Rams in the Driver’s Seat

Matthew Stafford has looked rejuvenated this season, orchestrating a passing attack that ranks third in the NFL in yards per game (267.5). A big reason is the emergence of Puka Nacua, who has been virtually unstoppable. Through four weeks, he leads the league in receptions (42) and yards (503). Against San Francisco specifically, Nacua has already torched them in limited matchups — clearing 92+ yards in two of three career meetings, including a massive 15-catch, 147-yard performance.

On the ground, Kyren Williams continues to be the engine that balances Sean McVay’s offense. He has topped 50 yards in three of four games and should see a steady workload if the Rams can build a lead early. Against a depleted 49ers front, the running lanes should open up even more.

San Francisco’s Concerns

The 49ers are dealing with injuries on both sides of the ball, and their biggest issue is a lack of pass rush. Without Bosa, San Francisco generated only five pressures last week against Trevor Lawrence — a concerning number heading into a matchup with Stafford, who thrives with time in the pocket.

Offensively, Brock Purdy returned from injury in Week 4, but his late-game fumble sealed San Francisco’s fate. Today San Francisco’s offense will be without Purdy which could mean it could be a long night for the Niners. Without Purdy, the 49ers’ offense loses rhythm and explosiveness. The backup options don’t inspire confidence, and on a short week, Kyle Shanahan may be forced to lean heavily on the ground game. Against a Rams defense ranked top-10 in EPA/play allowed, that’s a tough recipe to keep up on the scoreboard. If the Rams build a lead, San Francisco’s offensive limitations will be glaring.

Matchup Outlook

Historically, Kyle Shanahan has held the edge over Sean McVay (10-6 all time), but the circumstances here favor Los Angeles. The Rams are healthier, playing at home, and fielding one of the league’s most efficient offenses. On a short week, with San Francisco’s roster thin, it’s hard to see the 49ers keeping up if they fall behind early.

This sets up perfectly for a Same Game Parlay that leans into the Rams’ offensive stars and their overall edge at SoFi Stadium.

📌 Official Pick:
3-Leg SGP (-145)

• Los Angeles Rams Money Line

• Puka Nacua 6+ Receptions

• Kyren Williams 50+ Rushing Yards

The Rams’ formula is clear: feed Nacua through the air, let Williams handle the ground game, and trust Stafford to do his thing. Given San Francisco’s depleted defense, this parlay combines safety with value.

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