The resilience of P. vivax—the most widely distributed malaria-causing agent in humans— is in part due to its ability to form dormant liver forms called hypnozoites. These forms are capable of activating weeks, months, or years after an initial mosquito bite and are responsible for relapsing episodes that maintain transmission. The molecular signatures of hypnozoites and the hepatocytes they infect remain poorly understood due to technical challenges associated with liver-stages infections. To overcome technical limitations, we perform single-cell RNA sequencing to characterize host- and parasite- transcriptomic signatures. Using an in vitro liver stage system, we profile >1,000 P. vivax liver forms and the hepatocytes they infect. On the parasite’s side, we highlight distinct transcriptional signatures between schizonts and hypnozoites, and identify key differences in transcripts encoding for cellular fating RNA-binding proteins. On the host side, we uncover the transcriptional response of hepatocytes infected with either schizonts or hypnozoites. We show that while infection results in the enrichment of processes associated with energy metabolism and antioxidant stress response, the transcripts underlying these processes differ between schizont and hypnozoite infected cells. We also show that infection results in the down-regulation of pathways associated with host immune response, supporting the notion that P. vivax liver forms alter their host cell to remain undetected. Overall, our work offers insight into P. vivax biology—shedding light on transcriptome-wide signatures associated with the enigmatic hypnozoite—and reveals host- and parasite- markers that can serve as drug targets for new antimalarials.