This multiple case study qualitative research examined the impact of adoption and diffusion of innovation on Small and Medium Enterprises (SME’s) growth in the hostile business landscape of Khyber-Pakhtunkhwa, Pakistan. This research is intended to investigate research data and consequent findings based on an interview protocol that was purposefully developed from extant literature, complemented by an initial pilot study of two pharmaceutical SMEs. The researcher conducted 20 interviews, guided by the semi-structured interview protocol offered to the respondents beforehand after sorting their informed consent. The 20 participants represented the different hierarchal levels of the 08 case study of pharmaceutical from the two industrial clusters of Khyber Pakhtunkhwa, Pakistan, located at the Hayatabad Industrial Estate, Peshawar, and the Rashkai Industrial Estate, Nowshera. The analysis of the data presented findings and corroborated the research propositions that those SMEs that are structurally entrepreneurial and adopt innovation amenably, are open to mobility and tourism, yield satisfactory results in terms of their growth as compared to those that are inertial and unentrepreneurial. Similarly, the results offer confirmation that the effectiveness of government agencies that are explicitly formed to address the problems of small businesses is insufficient. They rather create hindrances than assistance due to the excessive delays in approving innovative ideas and conceptions by these related organizations and ministries. Moreover, the proposed framework offers pragmatic recommendations to contextualize entrepreneurial culture and innovative structures in SMEs and their essential factors in critical environmental circumstances.