This is going to depend on what you are trying to do.
Disclaimer: I'm going to make simplifications below.
A Zone is a thermal zone, and represents one cell of the overall calculation, where everything will have the same conditions. You can set internal gains (people, electric equipment, lights, etc), define HVAC equipment, set a specific thermostat, etc, and energyplus will also perform an energy/mass balance for that zone as a whole. (By default,) The zone will have the same air temperature throughout for example.
There is a helpful paragraph in the "E+ Essentials", see https://bigladdersoftware.com/epx/doc..., and another paragraph 'Zone' in https://bigladdersoftware.com/epx/doc...
Some rough examples:
If you have two bedrooms next to each other, and they are heated/cooled exactly the same way (same hvac equipment, same thermostat schedule), and you do not care about knowing specifically how much energy bedroom 1 versus bedroom 2 is using, then you can put both in the same thermal zone.
If you have an unheated garage next to a living room, then you probably shouldn't make them part of the same zone.
If you have a kitchen and a living room next to each toher, and there isn't a door in between or that door is always open, you can speculate they will be at the same temperature, so they should be part of the same zone probably.
