The valorisation of waste and by-products through microbial-based biotechnological solutions for more efficient re-use in the food industry represents one of the crucial issues in the green transition of food systems. Using apple, orange, tomato, broccoli, white cabbage, carrot, potato, buttermilk, scum, spinning water, and whey as model matrices and a panel of ten different lactic acid bacteria (LAB) strains (with a relevant representation of the species Lactiplantibacillus plantarum), we evaluated the combination of fast screening and digital solution as emerging approaches to optimise the management of the strains in the different matrices/conditions. For each matrix, the most interesting strain in terms of growth parameters was selected. The eleven stain/matrix combinations have been tested under specific conditions. After fermentation, we proposed a case study on re-use in the food industry, including the production of traditional fermented foods, innovative fermented foods, and as ingredients in non-fermented foods and beverages. In the framework of evaluating the feasibility of these optimisation strategies, different physical, chemical, and biological contaminants were studied to investigate the safety of the treated waste/by-products (e.g., pesticides, heavy metals, mycotoxins, and foodborne pathogens, for more than 100 contaminants). The assessment of contaminants did not detect the presence of contaminants outside the limits for the classes analysed. L.B. and GB received funding from Next-Generation EU [PNRR] in the framework of Component 2 Investment 1.3-Award Number: Project code PE00000003, Project title: “ON Foods-Research and innovation network on food and nutrition Sustainability, Safety and Security—Working ON Foods” (Cascade call, project 3SMicroBiotech4Food). V.C. is also supported by project code PE00000003. M.F. has received funding from PNRR Investment 1.4—D.D. 1032 17 June 2022, CN00000022] within the Agritech National Research Centre for Agricultural Technologies. M.L. is supported by INTelligent, ACTive MicroBIOme-based, biodegradable PACKaging for Mediterranean food – INTACTBioPack (PRIMA Section 2 Call multi-topics 2023 STEP 2).