Extracellular vesicles (EVs) and particles (EPs) are diverse micro- and nanoparticles that circulate in bodily fluids and can attach to, or be deposited onto, the extracellular matrix (ECM) and other surfaces. To date, the nomenclature and classification of matrix-bound or matrix-associated EVs and EPs (MEVPs) has been unclear, largely due to an apparent bias in the field towards EVs found in fluids and a lack of consensus guidelines. Recently, there has been a growing appreciation for several subtypes of MEVPs and their roles in applications ranging from wound healing to metastasis. However, progress in these fields has largely been achieved in silos, with minimal consideration for overlap or complementary function between different MEVPs. In this article, we briefly describe this growing field with a focus on heterogeneity and the lack of consensus, then discuss challenges and opportunities in improving MEVP isolation and characterization. Importantly, proteomic analyses of these unique MEVPs will be crucial in promoting rigor, reproducibility, and understanding in this exciting new field.