Organ-on-a-chip in vitro platforms accurately mimic complex microenvironments offering the ability to recapitulate and dissect mechanisms of physiological and pathological settings, revealing its major importance to develop new therapeutic targets. Bone diseases, such as osteoarthritis, are extremely complex comprising the action of inflammatory mediators leading to unbalanced bone homeostasis and de-regulation of sensory innervation and angiogenesis. Although there are models to mimic bone vascularization or innervation, in vitro platforms merging the complexity of bone, vasculature, innervation and inflammation are missing. Therefore, in this study we propose a microfluidic-based NeuroVascularized Bone chip (NVB chip) to 1) model the mechanistic interactions between innervation and angiogenesis in the inflammatory bone niche, and 2) explore as a screening tool of novel strategies targeting inflammatory diseases, using a nano-based drug delivery system. We were able to set the design of the platform and achieve the optimized conditions to address the neurovascular network under inflammation. Moreover, we validated this system by delivering anti-inflammatory drug loaded nanoparticles to counteract the neuronal growth associated with pain perception. This reliable in vitro tool will allow understanding the bone neurovascular system, enlightening novel mechanisms behind the inflammatory bone diseases, bone destruction and pain opening new avenues for new therapies discovery. This article is protected by copyright. All rights reserved.