This help page explains our shipping calculation settings in detail:
Unfortunately, we have no way to set up shipping rules according to ZIP codes; state-specific rules would be the closest you can do, in which case you could set up a rule for United States that covers the majority of states, then override that with rules for particular states.
Bear in mind that how you calculate shipping fees to charge your buyers does not have to match how you'd actually ship; you could just make sure your calculated fees at least cover your actual costs and pocket any excess to cover handling costs (packing materials, order processing and packing labor, etc.). E.g., you could just set up our USPS Priority Mail weight-based standard rate lookups, then whenever your Regional Flat Rate box would be cheaper, just ship with that method and pocket the difference; this would be the simplest approach we can recommend, and it would automatically stay in sync with current USPS Priority Mail standard rates.
If you'd still prefer to try approximating shipping costs for your 2 sizes of regional flat-rate boxes, you could pick 2 packaging types (e.g. Small Box and Regular Box) in Seller Admin > Cart Shipping Settings, then specify a Weight for those which equals your cheapest rates for those, then set up state-specific "Rate per unit weight" rules to multiply those by some factor when shipping to certain states (since Weight X Rate = the charges applied). States in Zones 1&2 would have a rate of 1.00, then states in Zone 3 would have a rate like 1.20, etc. This would get quite complicated to set up, and you'd need to redo all of this every time USPS changes their regional flat rates.