Sinonasal cancers (SNCs) are rare tumors, accounting for 3% of all cancers of head and neck district. Being rare and diversified in hundreds of subtypes, much is still to be understood to treat those tumors in a personalized manner. Despite being widely used, conventional in vitro 2D static cultures have significant limitations, such as the absence of the stimuli that cells perceive in native tissues. Growing cancerous cells onto porous biomaterial-based scaffolds and providing proper stimuli to reproduce the complexity of the tumor microenvironment (TME), can help to study cancer biology, test drugs and assess therapies in a better reliable way. Among these, organ-on-chips (OOCs) combine cells, biomaterial scaffolds and stimuli by providing a miniaturized and finely controlled 3D dynamic system, which can be observed in real-time [1]. Studying SNCs in a nose-on-chip platform could allow a better understanding of the mechanisms related to the tumor evolution, as well as an efficient and even personalized anticancer drug screening. In the present work, numerical simulations based on Computational Fluid Dynamics (CFD) were employed to simulate the laminar flow pattern to design a CFD-based nose-on-chip. Various chip configurations were investigated to replicate the interface between capillary blood flow and nasal respiratory epithelium. A porous zone was defined to simulate a 3D construct representing the respiratory epithelium colonized by cancer cells, mimicking the TME. Proper stimuli were chosen to ensure cell viability in this dynamic 3D culture. Therefore, different quantities of interest were evaluated, such as the distribution and residence time of cell nutrients, the elimination time of cell wastes and the distribution and residence time of microparticles, the latter potentially resembling injected drugs or immune cells. Numerical simulations played a pivotal role in assessing flow parameters challenging to evaluate in vitro, aiming to achieve a uniform and axial fluid flow to all cells and a time-accepted and homogeneous distribution/elimination of biological substances. The ultimate goal was to obtain the optimal chip design for SNC cell culture.