Microfluidic platforms represent a powerful approach to miniaturizing important characteristics of cancers, improving in vitro testing by increasing physiological relevance. Different tools can manipulate cells and materials at the microscale, but few offer the efficiency and versatility of light and optical technologies. Moreover, light‐driven technologies englobe a broad toolbox for quantifying critical biological phenomena. Herein, the role of photonics in microfluidic 3D cancer modeling and biosensing from three major perspectives is reviewed. First, optical‐driven technologies are looked upon, as these allow biomaterials and living cells to be manipulated with microsized precision and present opportunities to advance 3D microfluidic models by engineering cancer microenvironments' hallmarks, such as their architecture, cellular complexity, and vascularization. Second, the growing field of optofluidics is discussed, exploring how optical tools can directly interface microfluidic chips, enabling the extraction of relevant biological data, from single fluorescent signals to the complete 3D imaging of diseased cells within microchannels. Third, advances in optical cancer biosensing are reviewed, focusing on how light–matter interactions can detect biomarkers, rare circulating tumor cells, and cell‐derived structures such as exosomes. Photonic technologies' current challenges and caveats in microfluidic 3D cancer models are overviewed, outlining future research avenues that may catapult the field.

Biofabrication In article 2201442, Subhas C. Kundu, Rui L. Reis, and co‐workers explore the current landscape and potential future impact of photonics in microfluidic cancer modelling and biosensing. The manipulation of light within these miniaturized systems exposes unique opportunities where lightning‐fast interactions can both enable the fabrication of physiologically‐relevant 3D biological architectures and quantification of complex biological processes with unprecedented throughput towards data‐driven cancer research.