Recent findings in cancer therapy have revealed that both relative concentrations in drug combinations and the temporal sequence of delivery of anticancer drugs are crucial towards successful treatment and patient survival. Our group has investigated these parameters using Gemcitabine (GEM) and Doxorubicin (DOX) as a model anti-cancer drug combination. Synergy and drug scheduling were analyzed in detail to maximize growth inhibition of a 4T1 breast cancer model. We have developed peptide-based polymers that accurately carry synergistic ratios of GEM and DOX, and only one DNA-based aptamer. In addition, we have been able to reproduce optimized scheduled drug delivery of the drug combination to our cell model through hyaluronic acid (HA)-based drug conjugates. GEM and DOX are tethered to the HA-based conjugates through different stimuli-sensitive linkages affording different release rates from the polymer backbone. The resulting aptamer-peptide-drug conjugates and scheduled release polymer conjugates were tested in vitro and proved to be highly effective in inhibiting tumor growth of aggressive cancer cells (4T1). These studies therefore present novel methods to enhance the activity of traditional anticancer drugs via scheduled and synergistic delivery, and show great potential for future in vivo and clinical trails.