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However, traditional HCHTS in well\u2010plates often lack complexity of in\u2009vivo conditions. 3D cell cultures, like cellular spheroids\/organoids, offer a promising alternative by replicating in\u2009vivo conditions and improving the reliability of drug responses. Integrating spheroids\/organoids into HCHTS requires strategies to ensure uniform formation, systemic function, and compatibility with analysis techniques. This study introduces an easy\u2010to\u2010fabricate, low\u2010cost, safe, and scalable approach to create a bioinert hydrogel\u2010based inverted colloidal crystal (BhiCC) framework for uniform and high\u2010yield spheroid cultivation. Highly uniform alginate microgels are fabricated and assembled into a colloidal crystal template with controllable contact area, creating engineered void spaces and interconnecting channels within agarose\u2010based BhiCC through the template degradation by alginate lyase and buffer. This results in a multi\u2010layered iCC domain, enabling the generation of in\u2010vitro 3D culture models with over 1000 spheroids per well in a 96\u2010well plate. The unique hexagonal\u2010close\u2010packed geometry of iCC structure enables HCHTS through conventional plate reader analysis and fluorescent microscopy assisted by house\u2010developed automated data processing algorithm. 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