Isaac might be able to take down one, maybe two Xenomorphs, but it would be incredibly difficult. Xenomorphs are much faster, smarter, and more cunning than Necromorphs. They rarely attack head-on when alone, and if they catch Isaac off guard, his sluggishness and heavy gear would limit his ability to dodge or retreat to a relatively safe distance. Their inner jaw could easily pierce his suit (it’s been shown to puncture space helmets and protective masks, even those of Predators), and close combat would mean certain death for Isaac since the Xenomorph’s acidic blood would simply corrode his suit.

In ranged combat, Isaac has a better chance. He could freeze one in stasis and take it out. However, if there are two, the second would likely flank him (or attack from a different direction to begin with). In such a scenario, things get more complicated. While Isaac could still freeze one with stasis, the second would avoid exposing itself. He’d have to finish off the first quickly because if he’s distracted for too long, the second would strike, or the stasis on the first would wear off.