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They don't spawn randomly, there are certain spawn points. You'll learn where pretty quickly. The encounter always start with their leader running up to you and telling you that Caesar has decided you must die. If you kill the leader before he can deliver his message the rest of the group will become confused and will only attack if they can see you. This gives you a great opportunity to take them out from a distance. The upside of these encounters is that they provide a ton of valuables that you can sell, almost to a point where it feels like cheating.
When: The assassins will attack you every once every 24 in game hours in open areas in the wasteland, keep track of how much time is passing as it will keep them from catching you unprepared
Preparation: Turbo, 2 companions, Jury rigging, and a super sledge or thermic lance. You can get chems from the bartender in the lower brimstone at the Gomorrah) as well as a recipe for it from the first quest at the red rock canyon drug lab, and you can get cazador glands from the wind farm to the east of Old lady gibbons place near Novac. The assassins will always have one person with a super sledge or thermic lance so you can get that from looting them.
Take out the ones with the brush gun and 12.7 submachine gun first as those two are the ones dealing the most damage (if lower level assassins then it will be the ones with a hunting rifle and a 9mm or 10mm sub instead). Repair those weapons with cheap stuff using jury rigging and sell them for wild prices. Use the caps to buy better gear
They can be challenging at low-mid level, but over time they can go from a threat to basically free loot. Can get like 5k-10k each time they attack from repairing/selling their stuff