Improved sensitivity and continuous monitoring of therapeutic compounds are two of the most highlighted concerns for the treatment of malignant diseases, such as cancer. We demonstrated ultrasensitive screening of etoposide, a therapeutic compound widely-used in chemotherapy, achieved at low concentrations via the implementation of optimized graphene nanowalls. The developed graphene nanowalls displayed excellent electrochemical sensing capabilities in the etoposide detection with regards to the drug therapeutic window, without any post-transfer procedures or any further surface treatment. The direct, catalyst-free, vertical growth of graphene nanostructures forming a honeycomb network on the substrate, was presented involving three different substrates and implementing different growth parameters. SEM, TEM and Raman spectroscopy techniques were implemented to verify the results. The configuration that demonstrated the overall best performance in the sensing of electroactive compounds was selected and utilized for the effective screening of the drug resulting in a detection limit down to 4.36 nM. Moreover, the suggested sensors demonstrated excellent anti-fouling properties by removing in average the 97.44 ± 2.7% of first etoposide peak and 100% of second peak after 3 cycles of cleaning in blank buffer; bringing solutions to a common problem of electroactive compound screening and highlighting the sensing capabilities for continuous monitoring of the drug.