Podosomes and invadopodia are actin-based protrusions of the plasma membrane in metazoan cells, involved in cell adhesion to and degradation of the extracellular matrix (ECM). Key proteins include cortactin, (N)-WASP, Tks4, Tks5, and MT1-MMP. These structures are found in various cell types, including cancer cells, vascular smooth muscle cells, endothelial cells, and immune cells. Recent studies have advanced our understanding of their formation, function, and role in human diseases. Podosomes and invadopodia are characterized by an actin-rich core surrounded by adhesion and scaffolding proteins. They are regulated by multiple pericellular proteases, which facilitate ECM degradation. The formation of these structures is influenced by growth factors, integrin signaling, Src kinases, PKCs, reactive oxygen species (ROS), and microRNAs. Podosomes and invadopodia play crucial roles in cell migration, tissue remodeling, and immune surveillance. Their abnormal formation is associated with developmental disorders, vascular diseases, and cancer metastasis. Despite significant progress, many questions remain about their molecular differences, mechanics, and therapeutic potential.Podosomes and invadopodia are actin-based protrusions of the plasma membrane in metazoan cells, involved in cell adhesion to and degradation of the extracellular matrix (ECM). Key proteins include cortactin, (N)-WASP, Tks4, Tks5, and MT1-MMP. These structures are found in various cell types, including cancer cells, vascular smooth muscle cells, endothelial cells, and immune cells. Recent studies have advanced our understanding of their formation, function, and role in human diseases. Podosomes and invadopodia are characterized by an actin-rich core surrounded by adhesion and scaffolding proteins. They are regulated by multiple pericellular proteases, which facilitate ECM degradation. The formation of these structures is influenced by growth factors, integrin signaling, Src kinases, PKCs, reactive oxygen species (ROS), and microRNAs. Podosomes and invadopodia play crucial roles in cell migration, tissue remodeling, and immune surveillance. Their abnormal formation is associated with developmental disorders, vascular diseases, and cancer metastasis. Despite significant progress, many questions remain about their molecular differences, mechanics, and therapeutic potential.