The interactions between cells and their surrounding extracellular matrix (ECM) are dynamic and play critical roles in cell migration during development, health, and diseases. Recent advances have highlighted the complexity and diversity of ECM compositions, or “matrisomes”, of tissues resulting in ECMs of different physical, mechanical, and biochemical properties. Investigating the effects of these properties on cell-ECM interactions in the context of cell migration have led to a better understanding of the principles underlying tissue morphogenesis, wound healing, immune response, or cancer metastasis. These new insights into the interplay between ECM dynamics and cell migration can lead to the identification of unique opportunities for therapeutic interventions. •The matrisome is the set of genes encoding extracellular matrix (ECM) components.•The composition of the extracellular matrix is tissue-specific.•Tissue-specific matrisomes results in unique protein assemblies and ECM architectures.•ECM composition confers interdependent physical, mechanical, and chemical properties.•Changes in ECM composition, assemblies, and properties regulate cell migration.