Stays in Costello beyond Rio S. Lorenzo

Please be more specific about the location. Almost all of Sestiere Castello is beyond Rio San Lorenzo (meaning farther east). That's a very large area.

I wouldn't expect any safety issues at all.

I'd definitely plan to take a vaporetto from your entry point (the train station?) to the stop closest to your lodgings, but we need an address to tell you which one that is, and how bad a walk you'll have. In Venice it's important to zoom in on the map and figure out how many bridges you'll have to cross between the vaporetto stop and your lodgings. Sometimes there's no bridge where you wish one would be and you have to walk a few blocks out of your way, as well. It's not a good idea to just look at the distance between two places as the crow flies.

The eastern part of Castello is partly large buildings of no interest to tourists except during the summer Biennale and partly residential. There are some restaurants and small food stores, but they might be some distance from your lodgings, so again we need more specific information.

Ask how close it is to Campo San Lorenzo. Or ask for the actual address, which would be Castello plus a 4-digit number ( I.e., Castello 4358). That will pinpoint the actual location.

As acraven says, Castello is large, and the eastern end is far from shops,restaurants, and tourist sides.