The impact of blood and its factors on vector-borne diseases is significant and multifaceted yet understudied. While blood is expected to play a central role in transmission, pathogen development, vector behavior, and vector competence, in experimental settings, most studies are developed in the frame of a single, infected blood meal. To effectively combat vector-borne diseases, we need to determine what is the influence of insect blood-feeding behavior on transmission and development of pathogens, toward translation to natural field settings. This review summarizes current findings, highlights key gaps, and outlines future research directions to enhance our understanding of the role of blood in vector-borne disease transmission.