Tumor heterogeneity plays an important role in cancer progression. However, the mechanisms of how clonal diversity is generated within the tissue and how such diversity causes tumor progression are poorly understood. Here, we found in Drosophila eye imaginal disc that oncogenic cell clones expressing RasV12 or Src normally result in benign tumors but both develop into metastatic tumors when interact with each other. We found that Notch is upregulated in Src-activated clones while the Notch ligand Delta is upregulated in Ras-activated clones, leading to trans-activation of Notch signaling in Src-activated cells nearby Ras clones. Elevated Notch signaling in Src-activated cells causes tumor invasion cell-autonomously, while at the same time induces metastatic invasion of neighboring Ras-activated cells via upregulation of secreted growth factor Upd. Furthermore, we developed a mathematical model for cell population dynamics in the epithelium, in which Ras- and Src-activated clones exhibit proliferation and apoptosis depending on intercellular signaling between them. Through the simulation, we found that inter-clonal cooperation of Ras- and Src-activated tumors leads to expansion and persist activation of Notch and JAK-STAT signaling throughout the tissue, which generates highly heterogeneous cell populations with distinct oncogenic activities. This heterogeneity could cause symbiotic malignant tumors observed in the Drosophila imaginal discs.