Vermicompost has been promoted as a viable substrate component owing to its physicochemical properties, nutrient richness, and status as an excellent soil improver. It is considered the best organic fertilizer and is more eco-friendly than chemical fertilizers. Plant-growth-promoting microorganisms (PGPMs) are defined as plant biofertilizers that improve nutritional efficiency—that is, they transform nutrients within substrates from organic to inorganic forms, making them available for plants. The main objective of this research study is to evaluate the effects of the application of three PGPM microbial consortia on different mixtures of organic substrates based on vermicompost (V) and coconut fiber (CF) on two different horticultural crops. We performed a yield analysis and drainage nutrient tests and determined the plant nutritional status and enzymatic activity in organic substrates based on the two crops, Cucumis melo L. and Solanum lycopersicum L. A multivariate analysis of variance and principal component analysis was conducted using substrate types and PGPMs as factors. Differences (p < 0.05) in yield, dehydrogenase activity, the nutrient concentrations in a petiole sap, and drainage were observed at 30, 60, 75, and 90 days after transplant. PGPMs such as Trichoderma sp. and plant-growth-promoting rhizobacteria (PGPR) in organic substrates (40V + 60CF) can significantly improve the nutritional status of plants for use in organic soilless container agriculture. Biofertilization with PGPMs and suitable mixtures of organic substrates together with aqueous extracts (tea) of vermicompost, as nutrient solutions applied by fertigation, has allowed us to achieve an adequate level of production through environmentally friendly techniques. The results obtained allowed us to affirm that it was possible to replace conventional fertilization using no chemical products and ensure adequate crop nutrition by supplying main macronutrients with organic sources and biofertilizers.