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In the upcoming years, the world will face societal challenges arising, in particular, from the impact of climate change and the inefficient use of natural resources, in addition to an exponential growth of the world population, which according to the United Nations (UN) estimations will be 9.8 billion in 2050. This increasing trend requires optimized management of natural resources with the use of value-added waste and a significant reduction in food loss and food waste. Moreover, the recent pandemic situation, COVID-19, has contributed indisputably. Along with the agri-food supply chain, several amounts of waste or by-products are generated. In most cases, these biomass wastes cause serious environmental concerns and high costs to enterprises. The valorisation of the agri-food loss and food industry wastes emerged as a useful strategy to produce certain value-added compounds with several potential applications, namely in the food, health, pharmaceutical, cosmetic, and environmental fields. Therefore, in this review, some of the crucial sustainable challenges with impacts on the valorisation of agri-food loss/wastes and by-products are discussed and identified, in addition to several opportunities, trends and innovations. Potential applications and usages of the most important compounds found in food loss/waste will be highlighted, with a focus on the food industry, pharmaceutical industry, and the environment.