Lichens, symbiotic holobionts composed of fungi and photosynthetic partners, are a prolific yet underexploited source of unique secondary metabolites. This review synthesizes current research on lichen-derived compounds, including contributions from mycobionts, photobionts, cyano-bionts, and endo-lichenic fungi (ELF), emphasizing their significant capability across pharmaceutical, agricultural, cosmetic, and nanotechnological domains. We bring attention to evolving facets of lichen biology, such as the metabolic roles of cyano-bionts, the increasingly recognized role of ELF, the synergistic bioactivity of crude extracts, and the largely unexplored pesticide potential of specific compounds. Notably, lichen metabolites function as effective bio-reductants and stabilizers in the green synthesis of nanostructures including silver (Ag), gold (Au), zinc oxide (ZnO), titanium dioxide (TiO2), and hybrid graphene-based materials. These nanomaterials exhibit multifunctionality ranging from pharmaceutical relevance to photocatalytic pollutant degradation and environmental sensing, supporting sustainable technological applications. Furthermore, we critically assess advancements in culturing strategies such as axenic culture, ELF propagation, and tissue culture that enable metabolite production without depleting natural lichen populations, directly addressing biomass and conservation challenges. This review offers a forward-looking perspective that integrates classical lichenology with emerging tools in nanoscience, green chemistry, and biotechnology, establishing lichens as a powerful platform for next-generation innovations in healthcare, agriculture, and environmental restoration.