The persistent challenges faced by enterprises in Ghana are often attributed to a complex interplay between institutional structures and individual entrepreneurial action. Prior research has frequently examined these factors in isolation, lacking a holistic diagnostic that captures their dynamic interaction over an extended period. This study aims to provide a comprehensive, qualitative diagnostic of the principal challenges confronting businesses, specifically examining the navigation of structural constraints through entrepreneurial agency. A qualitative, multi-method design was employed, comprising 42 in-depth, semi-structured interviews with founders and senior managers, alongside a thematic analysis of archival business reports and policy documents. Purposive and snowball sampling ensured a diverse range of sectors and firm sizes. Analysis identified three core, interlinked thematic challenges: infrastructural deficits, access to finance, and regulatory bureaucracy. A dominant theme was the strategic, yet costly, agency entrepreneurs exert to circumvent systemic hurdles; for instance, approximately 70% of participants described creating parallel, informal systems to ensure reliable electricity supply. The findings illustrate that business challenges are not merely external constraints but are actively negotiated and reshaped through persistent entrepreneurial action, though often at a significant personal and financial cost to the enterprise. Policymakers should focus on co-designing interventions with business owners to address infrastructural gaps. Financial institutions ought to develop lending products recognising non-traditional collateral. A review of business registration and tax compliance procedures is urgently needed to reduce bureaucratic burdens. entrepreneurial agency, structural constraints, business environment, qualitative diagnostic, institutional voids This paper provides a novel, longitudinal diagnostic framework that synthesises institutional theory with entrepreneurial practice, offering a nuanced understanding of how structural challenges are perpetually navigated rather than statically endured.