All organisms exist within ecological communities where they encounter other species through a range of interactions, including competition for resources, cooperative or facilitative relationships, and coexistence within shared habitats. These interactions vary in duration, intensity, and specificity, and they can influence not only the ecological dynamics of communities but also the evolutionary pathways of the species involved. When interacting species impose selective pressures on one another, and those pressures lead to reciprocal and measurable evolutionary change, the process is known as coevolution. Research on coevolution has traditionally emphasized pairwise systems because they are more tractable for experimental and analytical study. However, natural systems often involve multiple interacting partners, and these multispecies associations can produce evolutionary patterns that differ from those observed in simpler pairwise models. Understanding the mechanisms that drive coevolutionary change, therefore, requires approaches that account for the complexity, context dependence, and historical depth of interactions among diverse taxa.This dissertation examines the evolutionary dynamics in a tripartite system comprising cacti, yeasts that inhabit necrotic cactus tissue, and Drosophila that feed on those yeasts. The system is found across arid regions of the Americas and provides a framework for examining how ecological interactions shape diversification across time and geographical space. By assessing broad evolutionary patterns spanning the last 30 million years, when these lineages first came into contact (Chapter 3), alongside a present-day example of their interactions (Chapter 1), this work traces the development of key ecological relationships and evaluates how these interactions have influenced the evolutionary history of the taxa involved. Chapter 1 investigates how cactus and yeast jointly affect Drosophila fitness in both field and laboratory settings. Cactophilic Drosophila, especially Drosophila mettleri, has primarily been studied in the field. This chapter establishes the foundation for studying this specialist system in a lab environment, and findings show D. mettleri relies on the host plant rather than environmental microbes. Chapter 2 reviews and synthesizes the evolutionary histories of each major lineage in the cactus-yeast-Drosophila system, providing an updated phylogenetic overview. Although this system has been examined for nearly fifty years, reconstructing phylogenies has remained challenging. This meta-analysis improves the resolution of previously published phylogenies and supports future systematic and evolutionary research. Chapter 3 evaluates evolutionary histories and associations for evidence of co-diversification. It assesses diversification rates within each lineage, compares rates through time, and reconstructs ancestral ranges to clarify how taxa dispersed and how geological events influenced their evolution. The results illustrate that members of this system experienced parallel evolutionary histories across both time and space. This chapter advances beyond traditional pairwise coevolutionary approaches toward a more integrative network-based framework. Together, the three chapters of this dissertation demonstrate how integrating ecological, phylogenetic, and macroevolutionary perspectives enhances our understanding of multispecies interactions. By examining both contemporary ecological dynamics and long-term diversification patterns, this work shows that the cactus-yeast-Drosophila system provides a valuable model for studying how ecological relationships develop, persist, and influence evolutionary outcomes across broad temporal and spatial scales. The findings highlight the importance of considering entire networks of interacting species rather than focusing solely on pairwise comparisons, as network-level approaches reveal shared historical patterns and clarify how ecological associations shape evolutionary trajectories. This integrated framework establishes a foundation for future research on multispecies coevolution and contributes to a broader understanding of how ecological complexity influences the diversification of life.