Lately, 3D cell culture technique has gained a lot of appreciation as a research model. Augmented with technological advancements, the area of 3D cell culture is growing rapidly with a diverse array of scaffolds being tested. This is especially the case for spheroid cultures. The culture of cells as spheroids provides opportunities for unanticipated vision into biological phenomena with its application to drug discovery, metabolic profiling, stem cell research as well as tumor, and disease biology. Spheroid fabrication techniques are broadly categorised into matrix-dependent and matrix-independent techniques. While there is a profusion of spheroid fabrication substrates with substantial biological relevance, an economical, modular, and bio-compatible substrate for high throughput production of spheroids is lacking. In this review, we posit the prospects of elastin-like polypeptides (ELPs) as a broad-spectrum spheroid fabrication platform. Elastin-like polypeptides are nature inspired, size-tunable genetically engineered polymers with wide applicability in various arena of biological considerations, has been employed for spheroid culture with profound utility. The technology offers a cheap, high-throughput, reproducible alternative for spheroid culture with exquisite adaptability. Here, we will brief the applicability of 3D cultures as compared to 2D cultures with spheroids being the focal point of the review. Common approaches to spheroid fabrication are discussed with existential limitations. Finally, the versatility of elastin-like polypeptide inspired substrates for spheroid culture has been discussed.