The main goal of MONALISA is to identify and promote the expansion of innovative and tailored solutions to prevent and reverse land degradation and desertification (LDD) while showcasing their socio-economic and environmental effectiveness. MONALISA will put in place a transdisciplinary approach to integrate scientific and local knowledge, emerging from newly and established social learning spaces with multi-sector stakeholders and multi-disciplinary and interdisciplinary researchers. Work will be carried out in six Mediterranean case studies (CS), encompassing different levels of aridity across five countries (European: Italy, Spain and Greece; and non-European: Tunisia and Palestine). In the CS, the following solutions to prevent and restore LDD will be assessed and scaled-out: (i) innovative grazing systems (e.g., adaptive multi-paddock grazing systems); (ii) microbial-based solutions (e.g., biofertilizers and symbiotic N-fixing rhizobia); (iii) conservation agriculture practices (e.g., cover crops and reduced tillage); (iv) ecological restoration practices (e.g., harvesting and seeding of residual plant materials in protected grasslands, green infrastructures); (v) water harvesting techniques; (vi) treated wastewater reuse in agriculture. One of the main outputs of MONALISA will be a multi-modular practice-oriented Decision Support System, composed of several web-based applications, that will leverage innovative data and technologies, including from remote sensing and Artificial Intelligence. MONALISA will focus on new business opportunities with (and not only for) stakeholders, taking into account cost-benefit and market analysis and the promotion of public and private investments. The main goal will be the promotion and adoption of sustainable and environmentally-friendly solutions for LDD while contributing to support the economic growth of European and Mediterranean drylands.