Bioengineered In Vitro 3D Cancer Models: A New Paradigm in Ethical and Predictive Oncology Research Toward Successful Pre‐Clinical Drug Screening

ABSTRACT The pharmaceutical industry is confronting a significant challenge due to the high rate of drug attrition, largely because of reliance on 2D cell culture and animal models for pre‐clinical validation. From this perspective, in vitro 3D cancer models offer a transformative tumor mimicry platform by enabling tunable and precise control over spatial organization and microenvironmental cues. Emerging advanced technologies such as 3D bioprinting, microfluidics, and multi‐organ‐on‐a‐chip systems have further enhanced the utility of these models for toxicity screening and accurate drug response prediction. This review comprehensively explores the various aspects of heterogeneity inherent within TME and their pivotal role in tumor progression, and determines the therapeutic outcomes. Special emphasis is placed on discussing diverse bioengineering techniques, evaluating their respective advantages and limitations, and the importance of integrative approaches to overcome the existing challenges. By recapitulating multifaceted aspects of the TME through hybrid bioengineering techniques, these platforms hold immense promise to improve predictive accuracy of pre‐clinical anticancer drug screening and accelerate the timeline for novel drug development. Overall, the adoption of bioengineered in vitro 3D cancer models offers a humane alternative with enhanced reproducibility and scalability compared to traditional models, thereby advancing ethical oncology research in alignment with the 3Rs principle.