Biosensor devices can constitute an advanced tool for monitoring and study complex dynamic biological processes, as for example cellular adhesion. Cellular adhesion is a multipart process with crucial implications in physiology (i.e. immune response, tissue nature, architecture maintenance, or behaviour and expansion of tumor cells). This work focuses on offering a controlled methodology in order to fabricate a flexible plasmo-nanomechanical biosensor placed within a microfluidic channel as a new tool for future cell adhesion studies. We designed, fabricated, and optically and mechanically characterized this novel optical biosensor. As a proof-of-concept of its functionality, the biosensor was employed to observe fibroblasts adhesion in a cell culture. The device is configured by an hexagonal array of flexible rigid/soft polymeric nanopillars capped with plasmonic gold nanodisks integrated inside a microfluidic channel. The fabrication employs low-cost and large-scale replica molding techniques using two different polymers materials (EPOTECK OG142 and 310 M). By using those materials the spring constant of the polymer nanopillars (k) can be fabricated from 1.19E-02 [N/m] to 5.35E+00 [N/m] indicating different mechanical sensitivities to shear stress. Therefore, the biosensor has the feasibility to mimic soft and rigid tissues important for the description of cellular nanoscale behaviours. The biosensor exhibits a suitable bulk sensitivity of 164 nm or 206 nm/refractive index unit respectively, depending on the base material. The range of calculated forces goes from ≈1.98 nN to ≈.942 μN. This supports that the plasmo-nanomechanical biosensors could be employed as novel tool to study living cells behavior.