I would make usage of Fallout 1/2 style random encounters, though with more meat and RP detail. Depending on the distance they're going to travel, you should prep a few before the session. Travelling should be difficult! They should need to think about what routes they take, how much food and water they have, etc. A character that invests in a skill like Outdoorsman/Survival should be rewarded by having this be their bread and butter.
Obstacles should also be somehting to keep in mind. Rivers that need to be forded, spots of radiation that could risk to taint the caravan's water supply (thereby lowering the value significantly from purified to a lower tier etc). Nests of buried radscorpions that will remain dormant as long as you don't put too much weight on the wrong area of sand. Perhaps even a minefield set up by an NCR platoon, carelessly left in order to kill Legion without any regard to other travellers that might happen across the road.
Finding out what the caravan's approach to raiders would be interesting too. Are they going to fight all of them? Or perhaps there's a "tax" pouch taken from the Caravan's supplies, extras kept just in case you guys need to provide "Tribute" to some tough looking road warriors along the way. Or maybe you could even earn the trust of some of the more reasonable raider-tribes an earn a rite of passage through their turf, maybe because you taught them how to cook the right chems or saved one of their kids from a Cazadore.
As for system stuff, I will shamelessly shill my own modification/version of the Fallout PnP: for content, ideas etc
