Time between resupply? Well, you can just take a bunch of resupply missions with you. Most stuff is packed ahead of time, except fresh veggies and fruits, but deep freezers can keep the nutritional value of those nearly as well as being fresh.
Redundancy/reliability? Bring the spare pool with you instead of keeping it on the surface for resupply flights. Bring two different systems.
Long duration life support? Enough mass allows you to avoid it all together if you like. This still has not sunk in to most of the fairly educated people who opine on this topic. Simple life support systems are VERY reliable, and the advantage of advanced life support systems is they reduce mass. If you don’t need the mass reduction, you don’t need the advanced life support.
Far from medical care? Small crew sizes are a mass constraint. More mass means you can afford large crews with dedicated medical personnel. And the equipment to go allow with it.
Also applies to radiation shielding (mass) and even partial gravity (centrifugal gravity is well known as a replacement but for some inexplicable reason is avoided… and yea, even short arm centrifuge is useful and could be used on the surface… the disorienting effects are actually manageable, and while in space, a tether can be used to enable long arm centrifugal gravity with little Coriolis effect).
Transit times can also be reduced significantly with refueling. 80-120 day transits are feasible, not just the most efficient 150-210 day transits for long stay. The surface of Mars also has significant radiation shielding in spite of the thin atmosphere. The Mars rover Curiosity measures the same radiation equivalent on Mars’s surface as on ISS today. Mars rover Perseverance also demonstrated production of unlimited oxygen from the Martian CO2 atmosphere using electricity. Regolith could also be used to enhance radiation shielding. This is before discussing water mining (and even that can be done without touching regolith, just the air using the WAVAR technique… useful for crew consumption although this method doesn’t scale up to producing enough for propellant very well).
There is no a single hazard or obstacle to a Mars mission that isn’t at least partially mitigated by having a lot more mass capability, ie a big and cheap reusable rocket (capable of landing on Mars and aerobraking).