Aging involves chronic organ degeneration, characterized by a continued decline in cellular regenerative ability and excessive buildup of extracellular matrix (ECM), leading to organ fibrosis. Fibrosis is now widely recognized as a key sign of organ failure, which has inspired new anti-aging strategies through antifibrosis treatments. In cancer, excessive ECM around and within tumors, known as desmoplasia, helps support tumor growth and malignancy. Age-related chronic inflammation and impaired tissue regeneration lead to a range of cell changes, which favor the development of fibroblast-like types, promote unchecked ECM buildup, and increased tissue stiffness. Notably, many mechanisms of aging closely overlap with those behind fibrotic progression. Understanding the critical cell groups, especially cancer-associated fibroblasts, could open promising options for anti-fibrotic and cancer treatments. The integration of progress in molecular medicine, traditional herbal therapies, and new technologies provides a powerful path for drug discovery and therapy development. In this review, we outline the main cell types and molecular pathways involved in organ aging and fibrosis. We also highlight the recent advances in anti-fibrotic Traditional Chinese Medicine (TCM) and gene and cell therapies in cancer and anti-aging research. Lastly, we examine the role of new technologies, including nanomedicine and organoid models, in the development and testing of drugs for anti-fibrotic therapies.