Assuming that regional settings can provide an essential level of economic coordination that goes beyond firmsí direct decisions and be a major source of region-specific material and non-material assets, this paper addresses the question of which kind of socio-economic regional-effects may explain different entrepreneurial behaviours? Empirically, the analysis is based on a questionnaire application to a sample of 167 small and medium sized firms from textile, clothing and leather (TCL) sectors, and belonging to the following European Southern areas: North (Portugal), Valencia (Spain), Macedonia (Greece) and South Italy (Italy). The selection of these regions was made considering their economic vulnerability, based on three major criteria: EU objective 1 status, being outside large urban centres and with an economic tissue based on labour-intensive firms. A common questionnaire was applied in each region, allowing a cross-country analysis among regions whose economic dependence to labour intensive sectors, is a common threat. Besides the strong commonalities among these four regional settings, it was possible to identify local/regional specificities that impact in the way firms respond to the new challenges coming from changing market conditions.