I will be returning from Rome to Florida, luggage checked thru. The flight lands in EWR too late to connect with the last flight to destination. Can I leave the checked baggage, after clearing customs, and go to a hotel ?
Probably not. I would ask the airline. Newark also a left luggage service
If you are booked thru on the same ticket your airline may allow you to do this. After you go thru customs there will be a spot where you can hand checked baggage back to the airline so if the airline says OK you can do that and be on your way.
If not, then just keep your luggage and head to a hotel.
editing to add: I think there are some airports where you ID your bags for the custom's officer on a screen but I've not flown thru Newark so I don't know if this is the case there or not.
ask the airline
That is where you will get an answer, not just speculation
Would you really want the airline to keep your luggage overnight? I know I would rather have it in my hands.