Nanomedicine formulations, such as liposomes, polymers and micelles, are extensively employed for anticancer drug delivery. By delivering drug molecules more efficiently to pathological sites and by attenuating their accumulation in potentially endangered healthy tissues, nanomedicines assist in improving the balance between chemotherapy efficacy and toxicity. Nanomedicines are furthermore increasingly used to enable to in vivo application of nucleic acid therapeutics, such as siRNA and DNA. The tumor accumulation of nanomedicines is traditionally ascribed the Enhanced Permeability and Retention (EPR) effect, which is highly variable, both in animal models and in patients, and both inter- and intraindividually. To overcome issues associated with tumor targeting heterogeneity, and to help improve the cancer nanomedicine clinical translation, we are working on systems and strategies to monitor and modulate tumor-directed drug delivery. In the present lecture, several of these strategies will be highlighted, including imaging-guided interventions to prime tumor blood vessels and the microenvironment, and the use of imaging and biopsy biomarkers for patient stratification, to thereby promote individualized and improved cancer nanomedicine treatment.