Earthworms are ecosystem engineers that play a vital role in soil structure, nutrient cycling, and ecological balance. Beyond their ecological importance, they exhibit remarkable regenerative potential, making them valuable models for studying cellular and molecular reprogramming. Regeneration in earthworms follows a coordinated sequence of wound healing, blastema formation, cellular proliferation, re-segmentation, and tissue growth. These processes are regulated by conserved gene networks and signalling pathways, including pluripotency-associated factors such as Sox2, Oct4, Nanog, Lin28, and c-Myc, along with developmental regulators like Hox and Wnt families. The clitellum serves as a reservoir of stem cells and regenerative factors (e.g., TCTP, Wnt3a, VEGF, YAP1), coordinating cell proliferation and morphogenesis. Species-specific differences exist: Eisenia fetida and Eudrilus eugeniae can regenerate both anterior and posterior segments, whereas Lumbricus terrestris shows limited capacity. Regeneration is influenced by intrinsic and extrinsic factors, with pollutants such as pesticides and heavy metals impairing gene expression and promoting oxidative stress. Understanding these molecular and ecological determinants highlights the dual significance of earthworms as models for regenerative biology and as indicators in ecotoxicology. This review synthesizes current knowledge and emphasizes future prospects for applying earthworm regeneration studies to biomedical and ecological contexts.