Humans are chronically exposed to airborne microplastics (MPs) by inhalation. Various types of polymer particles have been detected in lung samples, which could pose a threat to human health. Inhalation toxicological studies are crucial for assessing the effects of airborne MPs and for exposure-reduction measures. This communication paper addresses important health concerns related to MPs, taking into consideration three levels of complexity, i.e., the particles themselves, the additives present in the plastics, and the exogenous substances adsorbed onto them. This approach aims to obtain a comprehensive toxicological profile of deposited MPs in the lungs, encompassing local and systemic effects. The physicochemical characteristics of MPs may play a pivotal role in lung toxicity. Although evidence suggests toxic effects of MPs in animal and cell models, no established causal link with pulmonary or systemic diseases in humans has been established. The transfer of MPs and associated chemicals from the lungs into the bloodstream and/or pulmonary circulation remains to be confirmed in humans. Understanding the toxicity of MPs requires a multidisciplinary investigation using a One Health approach.