Microplastics were initially recognized and investigated primarily as aquatic contaminants, but they are now known to circulate among atmospheric, terrestrial, freshwater, and marine environments. Their significance therefore extends beyond their occurrence in individual environmental compartments. During transport, particles may undergo fragmentation, ultraviolet weathering, oxidation, contaminant sorption, and biological colonization, progressively modifying the physicochemical and biological characteristics of the material eventually encountered by organisms. This review examines microplastic pollution from a trajectory-aware perspective, in which environmental trajectory refers to the sequence of environmental compartments and transformation processes experienced by a particle between its source and the point of sampling or biological exposure. We propose that environmental risk should therefore be interpreted not only from polymer identity, particle size, or sampling compartment, but also from the “state of the particle at the point of exposure”. We synthesize evidence on microplastic sources, inter-compartment transport, environmental transformation, exposure pathways, and biological effects, with particular attention to the substantial variability reported among toxicological studies. Differences in particle properties, weathering history, associated contaminants, biological colonization, dose, exposure duration, analytical methods, and organismal characteristics may together explain why apparently similar studies produce divergent outcomes. This framework also highlights an important distinction between experimental reproducibility and environmental representativeness, since pristine commercial particles commonly used in laboratory studies may differ substantially from environmentally transformed microplastics. Airborne microplastics, ingestion and inhalation pathways, nanoplastics, and comparisons with historical particulate pollutants are considered within this broader context. We argue that future microplastic research should move beyond documenting where particles occur and increasingly determine how environmental trajectories shape particle state at exposure and, consequently, biological response.