The valorization of fruit-derived residues under the biorefinery concept has been a topic of interest in the last years due to the presence of high value-added substances in their composition. However, feasible alternatives for their implementation at an industrial level are still being developed since the abundance of pectin and extractives has made its biorefining challenging compared to conventional lignocellulosic residues. In this study, the sequential valorization of Orange Residues (OR) in a biorefinery was evaluated following the principles of biomass cascading and considering the composition of residual streams as a valuable input to maximize recovery after each processing step, without focusing on a sole product. To extract full value from the side-streams, fermentation with conventional and non-conventional yeasts was explored. The proposed biorefinery sequence produced essential oils, phenolic compounds, pectin, and fermentable sugars that were later converted to ethanol, xylitol, and single-cell protein. A detailed mass balance allowed to track compositional changes throughout the cascade and identify how extraction substances accumulate after each step, affecting further processing and side-stream utilization. The sequence proposed in this work extracted/transformed ∼85 % of the initial biomass into value-added products.