Thin film technology has emerged as a pivotal field with numerous industrial applications. Depending on their properties-such as magnetic characteristics, conductivity, architectural structure, stability, and functional backbones-thin films are widely utilized in optoelectronics, thin-film coatings, solar cells, energy storage devices, semiconductors, and separation applications. However, for all these applications, thin films must be securely attached to specific substrates, and substrate compatibility with both the thin film and the film-growth process is crucial for optimal performance. In this review, we emphasize the significance of growing thin films, particularly covalent organic framework (COF) thin films, on suitable substrates tailored for various applications. For separation technologies, polymer thin films are commonly fabricated on porous polymeric or metal-based membranes. In contrast, thin films of metals and metal oxides are typically deposited on conducting substrates, serving as current collectors for energy storage devices. Semiconductor thin films, on the other hand, are often grown on silicon or glass substrates for transistor applications. Emerging COF thin films, with their tunable properties, well-defined pore channels, and versatile functional backbones, have demonstrated exceptional potential in separation, energy storage, and electronic and optoelectronic applications. However, the interplay between COF thin films and the substrates, as well as the compatibility of growth conditions, remains underexplored. Studies investigating COF thin film growth on substrates such as metals, metal oxides, glass, silicon, polymers, ITO, and FTO have provided insights into substrate properties that promote superior film growth. The quality of the film formed on these substrates significantly influences performance in applications. Additionally, we discuss the stabilization of biological substrates, like peptide-based biomimetic catalysts and enzymes, which often suffer from instability in non-aqueous environments, limiting their industrial use. Growing COF membranes on these biological substrates can enhance their stability under harsh conditions. We also highlight techniques for growing COF membranes on biological substrates, ensuring the preservation of their structural integrity and functional properties.