Adhesion signaling involves interactions between cells and the extracellular matrix (ECM), which regulate cellular behavior. Integrins sense ECM properties and organize the cytoskeleton, while signaling pathways triggered by other receptors modulate cellular responses to growth factors. Recent studies show extensive crosstalk between integrins, Src-family kinases, and Rho-family GTPases in adhesion signaling. This review discusses the physical and functional connections between these proteins, focusing on how Src kinases mediate integrin signaling that regulates Rho-GTPase activation. Integrin engagement regulates Rho-GTPases, which control actin dynamics. Src kinases also regulate GEFs and GAPs that act on Rho-GTPases. The FAK-Src complex activates Rac1 and Cdc42, promoting membrane protrusion, while suppressing RhoA activity. This crosstalk is crucial for cell spreading, migration, and mechanotransduction. Integrins and Src kinases also regulate Rho-GTPases in processes like hemostasis, bone remodeling, phagocytosis, and tumor invasion. The balance between RhoA and Rac1 activities is essential for cell migration, with integrin-specific regulation controlling directionality. The FAK-Src complex regulates adhesion turnover and membrane protrusion during migration. Integrin signaling also influences ECM assembly, angiogenesis, and tumor growth. The stiffness of the ECM affects cell behavior, with integrins sensing matrix rigidity and regulating SFKs and Rho-GTPases. Understanding these crosstalk pathways is crucial for elucidating cellular processes and disease mechanisms.Adhesion signaling involves interactions between cells and the extracellular matrix (ECM), which regulate cellular behavior. Integrins sense ECM properties and organize the cytoskeleton, while signaling pathways triggered by other receptors modulate cellular responses to growth factors. Recent studies show extensive crosstalk between integrins, Src-family kinases, and Rho-family GTPases in adhesion signaling. This review discusses the physical and functional connections between these proteins, focusing on how Src kinases mediate integrin signaling that regulates Rho-GTPase activation. Integrin engagement regulates Rho-GTPases, which control actin dynamics. Src kinases also regulate GEFs and GAPs that act on Rho-GTPases. The FAK-Src complex activates Rac1 and Cdc42, promoting membrane protrusion, while suppressing RhoA activity. This crosstalk is crucial for cell spreading, migration, and mechanotransduction. Integrins and Src kinases also regulate Rho-GTPases in processes like hemostasis, bone remodeling, phagocytosis, and tumor invasion. The balance between RhoA and Rac1 activities is essential for cell migration, with integrin-specific regulation controlling directionality. The FAK-Src complex regulates adhesion turnover and membrane protrusion during migration. Integrin signaling also influences ECM assembly, angiogenesis, and tumor growth. The stiffness of the ECM affects cell behavior, with integrins sensing matrix rigidity and regulating SFKs and Rho-GTPases. Understanding these crosstalk pathways is crucial for elucidating cellular processes and disease mechanisms.