Plasmodium falciparum causes the most severe form of malaria and with emerging resistance to frontline treatments, there is the need to identify new drug targets in the parasite. One of the most unique processes in the parasite’s lifecycle is the invasion and subsequent egress of red blood cells (RBCs). This process is essential for parasite survival and proliferation which makes it an ideal drug candidate. During egress and invasion, many unique parasite ligands, receptors and enzymes are employed that could be druggable targets. To identify potential inhibitors we screened the Medicines for Malaria Venture (MMV) Pathogen Box, a 400 compound library comprised of drugs against neglected tropical diseases, including 125 with antimalarial activty. In the presence of the Pathogen Box compounds, we utilised transgenic parasites exporting the fluorescent reporter, Nanoluciferase (Nluc) to measure inhibition of parasite egress and invasion. By measuring the lack of Nluc activty released into the growth media from rupturing RBCs, we could detect inhibitors of egress. After completion of invasion, the ability of the inhibitors to block this process was quantified by measuring the Nluc activtiy in the newly invaded parasites. Drugs that killed intracellular forms of the parasites were removed from the hit list. At a concentration of 2 µM, we found 10 compounds that inhibited parasite egress >40% and 15 compounds that inhibited invasion >90%, the majority of these inhibitors with EC50’s of invasion in the nanomolar range. Thirteen of these egress and invasion inhibitors will be further characterised to identify how they inhibit parasites and what their biological targets might be with the long-term goal of developing some as future antimalarials.