ABSTRACT Breast cancer remains the most diagnosed cancer in women. Despite intensive work on new anticancer compounds, up to 90% of novel anticancer drugs do not progress beyond the clinical trial stage. This is since chemotherapy affects not only cancer cells, but also healthy tissues, leading to side effects such as cardiotoxicity or hepatotoxicity. Classical in vitro models do not reflect the body's complex physiology, especially fluidic environment and inter‐organ communication. Animal models do not always produce reliable results due to interspecies differences. In the following study, an advanced microfluidic multi‐organ‐on‐chip approach is used to analyze inter‐organ interactions and their impact on the response to a commonly used therapeutic substance. The applied solution allowed simultaneous study of therapeutic effects in three heterogeneous organ models: liver, breast tumor and heart. The use of four different culture configurations made it possible to assess the importance of interactions between organ models under microfluidic conditions. Based on the results, the influence of organ models on each other is noted, indicating that the designed microsystem allows assessment of inter‐organ interactions under conditions that better reproduce in vivo environment. Inter‐organ interactions affect aspects such as viability, metabolic activity, morphology, and effectiveness of the therapeutic substance, which is in line with the assumptions.