Cruise tourism is one of the fastest-growing segments of the global tourism industry, generating significant economic benefits while also creating challenges related to overtourism, congestion, environmental pressure, and residents’ quality of life. Understanding residents’ attitudes towards tourism is therefore essential for sustainable destination management. Although previous studies have examined the roles of place attachment and quality of life in shaping tourism attitudes, evidence from cruise destinations remains limited. This study investigates the influence of place attachment and quality of life on residents’ attitudes towards tourism in two contrasting European cruise destinations: Kotor (Montenegro) and Athens/Piraeus (Greece). Additionally, it aims to explore the link between place attachment and quality of life, which remains understudied in this context. The study also investigates whether destination moderates the effect between explored variables. To address this objective, Kotor and Athens/Piraeus were purposively selected as a maximum-variation pair. A quantitative survey was conducted among 319 local residents (157 from Kotor and 162 from Athens/Piraeus). The findings indicate that both place attachment and quality of life significantly influence residents’ attitudes towards tourism. Stronger place attachment was associated with more positive perceptions of social interaction with tourists and beneficial cultural impacts, but it also influenced residents’ attitudes indirectly through perceived quality of life. Moreover, place attachment was identified as a significant determinant across all five dimensions of residents’ quality of life. Furthermore, quality-of-life dimensions, particularly heritage and commercial development, socialisation and economic opportunities, and environmental conditions, emerged as significant predictors of tourism attitudes. Destination comparisons revealed overall consistency between both cruise tourism destinations, except for the link between place attachment and health and safety benefits, which was stronger among residents of Athens. The findings provide practical implications for sustainable tourism planning by highlighting the importance of incorporating residents’ perceptions into destination management.