The strategy of creating value and increasing the competitiveness of economic entities under the idea of sustainable development entails the need to provide access to up-to-date knowledge, which is to strengthen the decision-making basis and increase the level of properties of economic decisions. This argument strengthens the legitimacy of undertaking a research problem, oriented towards an overview of contemporary business challenges in the light of sustainable development, to assess the direction of activities undertaken by enterprises in the economic and socio-environmental sphere in connection with their activities. The need to undertake sustainable activities—with an emphasis on the environmental aspect—is particularly relevant to the pharmaceutical industry, which, in implementing activities oriented towards the protection of human health and life in connection with drug production, treats the issue of concern for the health of the planet as an extremely important challenge. The literature on the subject generally and insufficiently discusses sustainability issues for companies operating in this industry. Recognising the pharmaceutical sector as an area of economy of key importance in the socio-economic dimension at the level of national economies and at the international level, it became reasonable to scientifically identify the indicated issues in relation to pharmaceutical industry enterprises, with particular emphasis on entities operating in Poland. Hence, the main aim of the study, in response to the diagnosed gap, was to assess the directions of improvement of business models of Polish pharmaceutical enterprises, with consideration given to determinants of sustainable development. This study draws attention to the significance of practical choices of pharmaceutical entities—determined by their activity strategy, on sustainable development, as well as the impact of performance on the practice of sustainable development in the light of the assessment of the companies’ managerial effectiveness, demonstrating their significant importance. The realisation of the objective was based on a thorough review of the literature on the topic explored, as well as on the results of a diagnostic survey conducted among Polish pharmaceutical companies. An in-depth analysis of the findings in the area explored was conducted using statistical testing, including statistical ordering of variables, variable correlation matrix, logistic regression, odds ratio, and PQstat software. The main conclusion of the study is the finding that the business models of Polish pharmaceutical enterprises are continuously improving towards increasing the level of sustainable development, and the main determinant for the realisation of the above is the development of innovation, strongly correlated with the category of particularly good results on operations, constituting their managerial effectiveness.