The San Francisco 49ers and Los Angeles Rams face off again this week, and while the Niners took the first meeting, the rematch brings a new set of challenges, especially with a San Francisco defense that’s been hit even harder with injuries. If the Niners want to go 2-0 against the Rams this season, here are the keys to victory.

1. Keep the Run Game Rolling

With Christian McCaffrey healthy and in a rhythm, the ground game has to be the tone-setter. The Rams have struggled to stay consistent against the run this season, and if San Francisco’s offensive line can hold up and play the way they did last week against the Giants, they can control the clock and keep Matthew Stafford on the sideline.

2. Protect Mac Jones

Jones carved up the Rams earlier this year with quick reads and smart decision making, but LA’s front will look to create pressure and force mistakes this time around. The Niners’ offensive line will need to keep Jared Verse, and the rest of the Rams defensive line, from collapsing the pocket early. As long as Jones has time to operate, the offense can stay unpredictable.

3. Next Man Up on Defense

The loss of Mykel Williams to an ACL tear is a major hit for a defense already stretched thin. That means the younger depth guys, especially along the line, have to step up and play big time. The 49ers can’t let Kyren Williams and the Rams’ rushing attack find a rhythm, or it’ll open up everything for Stafford downfield.

4. Win the Turnover Battle

This rivalry often comes down to who makes the fewest mistakes. San Francisco’s secondary has been opportunistic all year, they’ll need that again against a quarterback who’s never been afraid to take chances. One takeaway could swing momentum in what should be a close divisional matchup.

5. Bend, Don’t Break Defense

With so many new faces stepping in, it’s unrealistic to expect perfection but resilience will matter most. Even if the Rams move the ball between the 20s, forcing field goals instead of touchdowns will be the difference. Holding strong in the red zone and keeping everything in front of them can turn what could be long drives into minimal damage for the 49ers.

Bottom line: If San Francisco controls the trenches and limits Stafford’s deep shots, they’ll be in position to stay atop the NFC West, have a shot at a playoff spot, and complete the season sweep of their division rival.