Exposure to atmospheric fine particulate matter (PM2.5) is currently recognized as a leading cause and/or a serious aggravating factor of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, and lung cancer. Notably, pulmonary-altered metabolism has emerged as an important hallmark of those diseases, while a growing body of evidence shows that exposure to PM2.5 deeply modulates the bioenergetic profiles and metabolic pathways of lung cells. Hence, there is great interest in understanding how PM-induced metabolic dysregulations may contribute to pulmonary pathobiological events. Herein, in vitro and in vivo studies assessing the impact of PM2.5 on lung cells metabolism are reviewed, with emphasis on lung bioenergetics and lipid composition. Overall, there is compelling evidence that the metabolism of lung cells is an early target of PM2.5 exposure, with changes in metabolic pathways being observed at PM doses that do not cause extensive cell death or tissue injury. Hence, characterizing metabolic dysregulations associated with specific PM features and exposure conditions represents a valuable approach to further enlighten the toxicity mechanisms of PM2.5 and to identify novel biomarker signatures of air pollution exposure and health hazard.