Fascia is a specialized connective tissue system that permiate, encapsulate, and interconnect between tissues and organs throughout the body. The fascia system regulates pain sensation, organ inflammation, trauma, and a fibrotic diseases. This mini-review summarizes recent findings from animal models, which reveal the inter-dependency between tissues/organs and the fascia system. special mechanisms of fascia response to skin inflammatory and fibrotic microenvironment via the dynamics within the fascia in trauma models, the functional heterogeneity of its fascia-born fibroblasts, and cellular communication, to highlight the significance of their stage-specific differentiation to disease progression. Understanding the molecular mechanisms and cellular processes within the fascia microenvironment, may serve as basis for future clinical translation.