Cell migration is a complex process that underlies tissue formation, maintenance, and regeneration, as well as pathological conditions like cancer. The migration mode of cells—whether individual (amoeboid or mesenchymal) or collective—depends on the extracellular matrix (ECM) and cell-specific factors such as adhesion, cytoskeletal structure, and proteolysis. A multiscale tuning model describes how ECM properties (dimension, density, stiffness, orientation) and cell determinants (adhesion, cytoskeletal polarity, proteolysis) interdependently control migration. Cells adjust their interactions with the matrix and each other to adapt to different environments, enabling both individual and collective migration. Amoeboid migration involves rounded or ellipsoid cells with minimal adhesion, while mesenchymal migration is characterized by elongated cells with focal adhesions. Collective migration occurs in cohesive multicellular units, such as sheets or tubes. The migration mode is influenced by ECM structure, cell adhesion strength, cytoskeletal dynamics, and proteolytic activity. For example, in 3D environments, cells may deform or remodel the ECM to navigate through gaps. ECM stiffness and orientation also affect migration, with cells tending to move toward stiffer substrates (durotaxis). Cell-cell adhesion determines whether migration is collective or individual. Strong adhesion promotes collective movement, while weak or absent adhesion allows for independent migration. Integrins and other adhesion molecules mediate cell-matrix interactions, influencing migration efficiency. Cytoskeletal dynamics, such as actin polymerization and myosin contraction, drive protrusion and retraction, enabling movement. Rac and Rho signaling regulate protrusion and retraction, with Rac promoting mesenchymal migration and Rho supporting amoeboid movement. Proteolytic activity, particularly by MT1-MMP, helps cells remodel the ECM to create pathways for migration. In some cases, cells deform or squeeze through narrow gaps without extensive ECM remodeling. The plasticity of migration modes allows cells to switch between individual and collective migration depending on environmental cues and cellular state. This plasticity is crucial in processes like cancer metastasis, where cells transition between different migration modes to invade tissues. The tuning model integrates multiple parameters that influence migration, allowing for a continuous rather than discrete adjustment of migration modes. This model highlights the interdependence of ECM and cell factors, providing a framework for understanding how cells adapt to different environments. Future studies will need to incorporate additional parameters and consider the complex interactions between different migration modes.Cell migration is a complex process that underlies tissue formation, maintenance, and regeneration, as well as pathological conditions like cancer. The migration mode of cells—whether individual (amoeboid or mesenchymal) or collective—depends on the extracellular matrix (ECM) and cell-specific factors such as adhesion, cytoskeletal structure, and proteolysis. A multiscale tuning model describes how ECM properties (dimension, density, stiffness, orientation) and cell determinants (adhesion, cytoskeletal polarity, proteolysis) interdependently control migration. Cells adjust their interactions with the matrix and each other to adapt to different environments, enabling both individual and collective migration. Amoeboid migration involves rounded or ellipsoid cells with minimal adhesion, while mesenchymal migration is characterized by elongated cells with focal adhesions. Collective migration occurs in cohesive multicellular units, such as sheets or tubes. The migration mode is influenced by ECM structure, cell adhesion strength, cytoskeletal dynamics, and proteolytic activity. For example, in 3D environments, cells may deform or remodel the ECM to navigate through gaps. ECM stiffness and orientation also affect migration, with cells tending to move toward stiffer substrates (durotaxis). Cell-cell adhesion determines whether migration is collective or individual. Strong adhesion promotes collective movement, while weak or absent adhesion allows for independent migration. Integrins and other adhesion molecules mediate cell-matrix interactions, influencing migration efficiency. Cytoskeletal dynamics, such as actin polymerization and myosin contraction, drive protrusion and retraction, enabling movement. Rac and Rho signaling regulate protrusion and retraction, with Rac promoting mesenchymal migration and Rho supporting amoeboid movement. Proteolytic activity, particularly by MT1-MMP, helps cells remodel the ECM to create pathways for migration. In some cases, cells deform or squeeze through narrow gaps without extensive ECM remodeling. The plasticity of migration modes allows cells to switch between individual and collective migration depending on environmental cues and cellular state. This plasticity is crucial in processes like cancer metastasis, where cells transition between different migration modes to invade tissues. The tuning model integrates multiple parameters that influence migration, allowing for a continuous rather than discrete adjustment of migration modes. This model highlights the interdependence of ECM and cell factors, providing a framework for understanding how cells adapt to different environments. Future studies will need to incorporate additional parameters and consider the complex interactions between different migration modes.