This study aimed at examining the adjustment of students with learning disabilities (LD) and at exploring the mediating role of hope. By means of a multidimensional approach, the interactions between risk and protective factors emerging from internal and external resources among 856 high school students (10th to 12th grades) were analyzed. A total of 529 typically achieving students and 327 students with LD attending general education classes in seven high schools completed seven instruments measuring sense of coherence, basic psychological needs, loneliness, family climate, hope, academic self-efficacy, and effort. The students’ achievements in English, history, and mathematics were collected. The analysis used structural equation modeling, and the results emphasized the significant role of hope as a mediator between risk and protective factors and academic self-efficacy and its significance for students with and without LD in explaining achievements and effort investment.