There are numerous hurdles hindering the clinical translation of nanomedicines. The major challenges are: reproducible manufacturing and scale-up, availability of appropriate characterization methods, instability under in vivo environments, safety issues, poor understanding of the disease heterogeneity and patient preselection strategies, regulatory barriers and inadequate understanding of the biophysical and chemical interactions of nanoformulations. Thus, a better understanding of key physicochemical attributes and their characterization methods, in vivo behavior and the in-vitro–in-vivo characterization cascade of stability, safety and efficacy testing is needed to accelerate nanomedicine translation. Technologies such as quality-by-design, process analytical techniques and microfluidics could significantly accelerate the translation of nanomedicines. However, these approaches require further learning and an adequate regulatory background. Overall, to achieve an efficient clinical translation, collaboration among academia, industry and regulatory bodies is required to ensure safe and effective nanomedicine products. This review discusses the challenges and opportunities to facilitate the translation of nanomedicines to a commercial product.