Why does the same oncogenic mutation drive tumor formation in some tissues but not in others? While cancer driver mutations are well documented, their tissue specific effects remain largely attributed to genetic factors, leaving the biophysical aspects underexplored. Here, we demonstrate that mechanical interactions, specifically interfacial tension between newly transformed and wildtype epithelial cells are critical in determining survival and growth of HRasV12 oncogenic mutants in human mammary and bronchial epithelia, leading to contrasting outcomes in the two tissues. In mammary epithelium, isolated oncogenic cells are extruded, a typical mechanism of defense against cancer in epithelia, while oncogenic groups become spatially confined in a kinetically arrested, jammed state, marked by an actomyosin belt at the interface. In contrast, bronchial epithelium permits persistent spreading of the same oncogenic cells, which form long protrusions regardless of colony size. Furthermore, oncogenic clusters in these two tissues exhibit distinct biophysical properties, including variations in cell shapes, intracellular pressure, cell to cell line tension, and cellular motility. Using a cell shape tension coupled bidisperse vertex model, we reveal that differences in interfacial tension at mutant cell and wild-type cell boundaries dictate whether oncogenic cells are eliminated, restrained, or expanded and that modulating interfacial tension alters mutant cell fate within the epithelium. Together, our findings uncover a mechanical basis for tissue-specific oncogenesis by highlighting how differential cellular mechanics at the oncogenic and host cell interface regulate tumor initiation and progression.