Basically: intonation and action. I'll explain.
Guitars are made of wood, an organic material, which is very susceptible to environment changes (humidity and temperature). So, after time passes, the wood may expand or contract, which changes the physical parameters of the guitar.
There are two forces at play: when tuned, the strings exert force pulling the fretboard "up". In most guitars, there's a long screw inside the fretboard, which pulls it "down".
"Tuning" a guitar means that the strings produce the right frequencies when plucked "open" (i.e. no fret pressed). Correct intonation means that the notes are still "in tune" (producing the right frequencies) along the frets of a same string. "Action" is the height between the string and the fret in different places at the fretboard (so, if you want to be precise, you'd say "6th string action at the 12th fret").
Action is mostly a matter of preference - lower means it's easier to fret the notes, higher means the strings ring out more freely, and therefore the notes sustain better. Can't go too low, or you'll start to experience "fretting" - the strings hit neighbor frets while vibrating for a note, producing an unpleasant metallic buzz.
The actual physical parameters which influence intonation and action are basically neck bow/relief and string length (via small metal pieces in the bridge of the guitar which can be moved, if you guitar has them). This is what the luthier (the professional who sets up instruments) interferes with.
This is a general view - some guitars may have additional factors to consider. For example, in floating bridge electric guitars, you'd need to consider the bridge springs tension as well, for they will influence both string action and the whammy bar travel.