Fungal cell factories serve as a robust platform for sustainable biomanufacturing, owing to their unparalleled metabolic diversity, enzymatic properties, and resilience to diverse environmental conditions. Recent advances in fungal biotechnology have vastly enhanced the potential for fungi to be used in the production of renewable bioenergy and functional biomaterials. Concurrent advances in systems biology, metabolic engineering, and synthetic biology have enabled the fine-tuning of metabolic fluxes to facilitate the enhanced biosynthesis of biofuels, including bioethanol, biodiesel, biogas, and biohydrogen, as well as mycelium-derived biopolymers. The lignocellulolytic fungi like Trichoderma reesei, Aspergillus niger, and Phanerochaete chrysosporium have been the main organisms of focus with respect to engineering, which enhances hydrolytic enzyme excretion, growth on substrates, and redox balance in these fungi. This engineering work parallels a new ability in omics technologies and CRISPR–Cas genome editing, permitting the facilitation and identification of regulation of biosynthetic gene clusters responsible for lipid accumulation, secondary metabolite production, and nanomaterial synthesis in fungi. Furthermore, new fungal-derived biomaterials have been reported, such as chitosan, β-glucans, and mycelium composites, which have been advanced as biodegradable alternatives to plastics and building materials derived from petroleum. This review critically reviews some of the more recent developments in respect of the reprogramming of fungal metabolism, process intensification strategies and integrated biorefinery applications. This will illustrate the convergence of fungal systems biology with the principles of circular bioeconomy and point out the technological, economic, and regulatory bottlenecks which need to be overcome to fully realise the potential of fungi as the biofactories of the future for the sustainable production of energy and materials.