This chapter focuses on the role of self-employment, exploring how the optimal allocation of human resources impacts crucial economic dynamics such as efficiency, productivity, and social inequalities. In this perspective, the labor market emerges as the contact point between macroeconomic trends and individual/social well-being. It is emphasized that production decisions and locational choices are interconnected—being influenced both by the internal organization of companies and the external environment, which evolves with the interaction of economic operators. Self-employment represents not only an alternative to salaried employment but also a catalyst for local economic growth. Individuals who opt for this path contribute to the diversification of the economy and can stimulate the demand for local goods and services, creating a positive multiplier effect. In contexts characterized by scarce opportunities for salaried employment, self-employment allows individuals to create their own jobs rather than seek them. This type of employment promotes innovation and flexibility, enabling entrepreneurs to adapt quickly to market changes, and introduce new ideas and technologies that improve the productivity and competitiveness of local businesses. However, the differences between urban and rural areas are significant. In cities, self-employment tends to reflect more innovative entrepreneurship, thanks to greater access to financial resources, a highly skilled workforce, and well-developed support networks. Cities offer a large and diversified market, increasing the chances of success for new products and services. Intense competition in urban contexts pushes entrepreneurs to innovate constantly to stand out from competitors, creating a dynamic environment that fosters economic development. In rural areas, self-employment often represents a response to the lack of opportunities for salaried employment. In these areas, markets are less diversified, and financial/technical resources are harder to come by, making it less innovative and more subsistence-oriented. Transportation costs and distance from economic centers increase the challenges for rural entrepreneurs, who face significant hurdles to compete with urban businesses. However, self-employment in peripheral areas can play a crucial role in enhancing local resources and preserving cultural and artisan traditions, creating unique market niches.