Like all pathogenic infectious agents, Plasmodium falciparum, the deadly malaria parasite, modulates its host environment as a part of its evolutionary adaptation to thrive, proliferate, and ultimately sustain its transmission. During their asexual intraerythrocytic developmental cycle, the parasites remodel the cytoplasm and surface of the host red blood cell (RBC) and alter its deformability. There is, however, also growing evidence that Plasmodium engages, modifies, and imports specific RBC proteins to facilitate specific biological functions essential for its growth and development within the human host. Although most mechanistic elements behind these processes are poorly understood, targeting the host proteome engagements to design host-directed antimalarial therapy has been stipulated for many decades. Here, we review research characterizing various roles of the erythrocyte proteome for the blood stage development of P. falciparum and discuss its potential for novel malaria intervention strategies.