1. To be particularly ineffectual, insubstantial, or unsuccessful. The high production value means that the film is visually stunning, but no amount of aesthetic beauty can save a film whose paper-thin plot runs on empty from start to finish. The former president promised quite a lot in his campaign speeches, but his administration ran on empty throughout his time in the White House.

2. To continue to operate with no or very little enthusiasm, energy, or resources left. (Usually used in the continuous tense.) I've been painting the house for four hours every night after work, and I am seriously running on empty at this point. We were running on empty by the time our team made it to the championship round.