There is increasing interest in repurposing by-products and residues from agricultural and agri-food industries, supporting environmental, social, and economic sustainability. Wineries and distilleries, an important segment of EU agriculture, generate substantial levels of waste annually with grape marc, a significant by-product of these industries, representing both an environmental challenge and an untapped resource. To achieve the sector's 2050 zero-waste vision, innovative waste management strategies are crucial. This review aims to explore the potential of grape marc as a natural source of high-value compounds and its conversion into a portfolio of high-value added bio-based products. The review discusses grape marc generation and the associated waste management challenges within the wine and distillery industries. It highlights innovative biological, thermal, and chemical conversion strategies for turning grape marc into high-value products. Additionally, it provides an overview of the main components of grape marc and explores its wide range of alternative applications, with particular emphasis placed on nutraceuticals, functional food and feed, biofuels, biomaterials, and agricultural amendments. In addition, the study highlights the integration of grape marc into a fungal-based biorefinery system, as promising upcycling strategy to drive innovation in the development of bio-based products, enabling a transformative waste-to-resource pathway. The findings support the advancement of innovative and feasible valorization models, contributing to sustainable waste management practices within circular economy framework.