The high failure rate of anticancer drugs in clinical trials highlights the need for preclinical models that accurately reproduce the structural, biochemical, and mechanical complexity of human tumors. Conventional two-dimensional cultures and animal models often lack the physiological complexity required to predict clinical outcomes, driving the development of three-dimensional systems that better emulate the tumor microenvironment. Among these, microfluidic-based spheroid models have emerged as powerful tools for cancer research and drug screening. By integrating 3D spheroids with microfluidics, these platforms allow precise control of nutrient flow, oxygen gradients, shear stress, and interstitial pressure, while supporting co-culture with stromal, immune, and endothelial cells. Such systems enable the investigation of drug response, angiogenesis, metastasis, and immune interactions under dynamic and physiologically relevant conditions. This review summarizes recent advances in microfluidic spheroid models for cancer, covering both carcinomas and sarcomas, with an emphasis on device design, biomaterial integration, and translational validation. Key challenges remain, including technical complexity, scalability constraints, and the absence of standardized protocols. Overall, the merger of microfluidic technology with 3D spheroid culture provides a promising pathway toward predictive, ethical, and personalized preclinical testing, bridging the gap between in vitro modeling and clinical oncology.

The advancement of personalized treatments in oncology has garnered increasing attention, particularly for rare and aggressive cancer with low survival rates like the bone tumors osteosarcoma and chondrosarcoma. This study introduces a novel PDMS–agarose microfluidic device tailored for generating patient-derived tumor spheroids and serving as a reliable tool for personalized drug screening. Using this platform in tandem with a custom imaging index, we evaluated the impact of the anticancer agent doxorubicin on spheroids from both tumor types. The device produces 20 spheroids, each around 300 µm in diameter, within a 24 h timeframe, facilitating assessments of characteristics and reproducibility. Following spheroid generation, we measured patient-derived spheroid diameters in bright-field images, calcein AM-positive areas/volume, and the binary fraction area, a metric analyzing fluorescence intensity. By employing a specially developed equation that combines viability signal extension and intensity, we observed a substantial decrease in spheroid viability of around 75% for both sarcomas at the highest dosage (10 µM). Osteosarcoma spheroids exhibited greater sensitivity to doxorubicin than chondrosarcoma spheroids within 48 h. This approach provides a reliable in vitro model for aggressive sarcomas, representing a personalized approach for drug screening that could lead to more effective cancer treatments tailored to individual patients, despite some implementation challenges.