Nanomedicine has emerged in the last few decades as a field that can significantly impact the diagnose and therapy of human diseases. [1,2] Based on the outstanding properties that materials acquired at the nanoscale, such as high surface-to-volume ratio, high physicochemical stability, high charge carrier mobility and biocompatibility, a variety of nanoformulations have been developed to be applied in medicine by tailoring their size, shape, charge, and surface functional groups. [2,3] Based on those properties, the design of multifunctional nanoparticles (NPs) for nanomedicine is one of the most promising and exciting research areas that is expected to revolutionize the medical field in the next few decades. [4] Some of these multifunctional NPs have the potentiality to combine both diagnosis and therapy, the so-called theranostics, which is one of the ultimate goals of this field to achieve personalized and precise medical care (Figure 1). Among the therapeutic techniques, nanomaterials developed for drug delivery purpose have been widely investigated as smart drug nanocarriers capable to target tumor cells, protect drugs from degradation, enhance drug solubility, improve biodistribution, extend drug life cycle, and prevent lethal side-effects to healthy tissues and organs. [2,3] The design of these smart drug delivery systems can be engineered to target a specific location by taking advantages of the host environment, using for instance antibodies, aptamers or peptides; and then react autonomously as stimuli-responsive drug release agents, triggered by endogeneous chemical reactions (e.g., enzymes, pH, hydrolysis) or exogeneous stimulisensitive mechanisms (e.g., near infrared light, temperature raise induced by an alternating magnetic field, among others). [5] Comprehensive reviews on the topic of smart nano-based drug delivery systems can be found elsewhere. [5,6] Further complex functionality is represented by smart theranostics, which hold high promise for the nanomedicine of the future. Next, recent representative examples from the research arena are described. Cai et al. [7] make use of enzyme-responsiveness to design a cathepsin B-sensitive theranostic agent. They synthesized a biodegradable conjugate composed of a Gd chelate (Gd-DOTA) as a T1-magnetic resonance imaging (MRI) contrast agent, Despite the progress achieved in nanomedicine during the last decade, the translation of new nanotechnology-based therapeutic systems into clinical applications has been slow, especially due to the lack of robust preclinical tissue culture platforms able to mimic the in vivo conditions found in the human body and to predict the performance and biotoxicity of the developed nanomaterials. Organ-on-a-chip (OoC) platforms are novel microfluidic tools that mimic complex human organ functions at the microscale level. These integrated microfluidic networks, with 3D tissue engineered models, have been shown high potential to reduce the discrepancies between the results derived from preclinical and clinical trials. However, ...