I dont think it needs to be online the whole time, but at least at the beginning, since the authentication is done through Steam.
I remember once I had an issue with my connection, and couldnt start it 😞
But maybe there is a workaround.
Also, I've read somewhere that this version of Substance Painter will be the very last on steam. So far, some of the updates were for free after a year of the initial purchase, but this one will be the last 😞