So far I haven't found a way (callback?) to tell when the last sample is out of the flowgraph. I am using the C++ API of GNU radio.
The wait() method of a top_block will block the calling thread until all items have passed through.
Note that this will only succeed if your source blocks indicate there are no more items, by returning -1 (gr::block::WORK_DONE). Vector and file sources and other such standard fixed-length sources do, but if your source is merely emitting no items at this time (e.g. a network source that's not currently receiving packets) the flow graph will still be running waiting for more. I do not know of a way to ask for "when all buffers are currently empty", if that's what you need.