Depression and anxiety significantly contribute to the global disease burden among adolescents, making culturally adapted measurement tools essential for effective resource allocation and program implementation. This study focused on adapting and validating the Patient Health Questionnaire for Adolescents (PHQ-A) and the Generalized Anxiety Disorder scale (GAD-7) within the diverse cultural context of Kathmandu, Nepal. Through ten focus group discussions, 25 cognitive interviews, and a cross-sectional survey of 413 adolescents, the study made critical cultural modifications to the instruments, such as converting statements into questions and employing a visual response scale. Results demonstrated that while the PHQ-A exhibited acceptable sensitivity and specificity for detecting depression, the GAD-7 showed lower effectiveness for anxiety, leading to higher false positive rates. These findings underscore the necessity of adjusting screening cut-offs to avoid overestimating prevalence rates in population studies and emphasize the importance of tailoring mental health screening tools to local cultural contexts.