Yes, it has to do with the destination. For example, a local or peddler freight will have its cars assembled in the order that they will be dropped off.
Like Dennis said, destination was the primary driver. Suppose a train originates at Yard A and runs to Yard D with stops at Town B and Town C in between. Leaving Yard A, the train would have all cars for Town B directly behind the locomotive, cars for Town C behind those and cars for Yard D at the rear. Depending on your era, there might be special rules for specific types of cars (such as no hazardous materials cars within 2 cars of the locomotive or caboose).
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