Scholars conducting cross-cultural research in mental health often import intervention programs found to be efficacious in one social context (e.g., Western) and directly implement them in other contexts (e.g., African and Asian) without recourse to the sociocultural disparities between the target populations and the theoretical foundations of the constructs and principles underpinning the intervention programs. Such efforts mistakenly assume that positive psychology interventions (PPIs), most of which were developed from Western perspectives and assumed individualistic cultural orientation and value systems, operate equally across all contexts. Drawing on the extant literature and on insights from designing, implementing, and evaluating group-based (mental) health behavior change intervention programs across several communities in Ghana, we discuss some sociocultural, theoretical, and methodological issues that can significantly constrain the design, uptake, and effectiveness of PPIs in the rural, low literate, socioeconomically disadvantaged, highly collectivistic context of Ghana, and sub-Saharan Africa more generally. In all illustrations, we offer suggestions to guide the design and implementation processes to ensure culturally appropriate, highly acceptable, and potentially effective intervention programs. We argue that PPIs can be potentially fructuous in the sub-region when adapted to, or embedded in, the cultural values of the target population and tailored to the needs, capacities, and circumstances of participants.