San Francisco’s run defense faces its toughest test yet as injuries along the 49ers defensive line raise big questions ahead of their Week 3 battle against the Arizona Cardinals. Despite opening the season 2-0 with dominant wins, cracks have shown against ground threats like De’Von Achane, and the challenge intensifies with Arizona’s dynamic duo of Jeremiyah Love and Tyler Allgeier splitting carries. Can Nick Bosa and Keion White compensate for shorthanded reinforcements inside? With CJ West on injured reserve and newcomers Naquan Jones and McKinnley Jackson pressed into significant roles, fans will get their first glimpse of how the 49ers adapt on the fly. Facing a Cardinals offense bolstered by Michael Wilson, Marvin Harrison Jr., and Trey McBride, San Francisco must balance stopping the run while not getting burned outside. All eyes are on whether these fresh faces can step up—and if the 49ers defense finds answers before the NFC West race heats up.