The San Francisco 49ers eye a 4-0 start as they clash with the Denver Broncos at Levi’s Stadium, capitalizing on a glaring matchup advantage: Denver's struggling run defense. With Christian McCaffrey set to exploit a Broncos unit ranked dead last in EPA per play against the run and notorious for missed tackles, the stage is set for a ground-game showcase. Key questions loom around 49ers wide receivers like Mike Evans and Brandin Cooks, amplifying the focus on McCaffrey and the dynamic San Francisco backfield. Defensively, the 49ers aim to remain the league's top unit at limiting explosive plays, but Marvin Mims returns for Denver, bringing elite speed and downfield threat potential. Can the 49ers secondary shut down Mims and adapt to possible new wrinkles from the Broncos’ offense? All eyes are on how the San Francisco defense and the Denver pass rush respond as these two powerhouses battle in a pivotal early-season NFL matchup.