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stimuli. Simultaneously, they support high-throughput drug efficacy screening with
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real-time resolution of pharmacokinetic/pharmacodynamic relationships . Despite

these advantages over animal models, organ-on-a-chip technology faces persistent
challenges including fabrication scalability limitations, material biocompatibility

constraints, and the need for advanced sensor integration—all requiring further

optimization to achieve clinical predictive validity 25,26 . (3) Tumor Spheroids: Uniform,

high-throughput multicellular spheroids permit drug screening under physiologically

relevant conditions. The development of tumor spheroids can be precisely controlled in

terms of size and composition through continuous perfusion using microfluidic

technology 27–29 . Additionally, integrating 3D-printed scaffolds with microfluidic

control enables precise generation of tumor stem-like spheroids with enhanced

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physiological relevance . These spheroids simulate solid tumor 3D structure while
retaining CSC characteristics. They exhibit in vivo-like cellular complexity, critical

cell-cell interactions, ECM deposition, and chemical gradients that restrict drug

diffusion to levels comparable to human tissues 27,31 . Spheroids also serve as models

for evaluating drug sensitivity and resistance, typically displaying heightened resistance
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to chemotherapy and radiotherapy versus 2D monolayers . They enable analysis of
growth constraints like oxygen tension, nutrient deficiency, radiation effects, and

angiogenesis 33,34 . Therefore, convergent advances in 3D bioprinting and tumor-on-a-

chip technologies are yielding biomimetic tumor models with unprecedented clinical

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relevance . 3D printing facilitates personalized manufacturing, complex structure
construction, and cost reduction 36,37 . Microfluidics dynamically simulates the TME,

enables high-throughput drug screening, and precisely controls physicochemical

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conditions . Integrating these technologies enhances tumor model humanization and
clinical translation, evidenced by successes in tumor-on-a-chip and drug delivery

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applications (summarized in Table 1).

Existing reviews typically examine microfluidics or 3D printing in isolation,

lacking systematic analysis of their synergistic convergence for oncology applications.
This review comprehensively elucidates advancements and prospects in integrated

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