Mentorship lies at the heart of effective missionary ministry, yet contemporary challenges— such as secularization, cultural resistance, and resource limitations—threaten its sustainability. This study examines Jesus’ mentorship model in Mark 3:13-19 as a paradigm for addressing these obstacles. Through exegetical analysis, the paper highlights Jesus’ intentional selection of the Twelve, His emphasis on relational discipleship ("that they might be with Him"), and His empowerment of them for mission ("He sent them out to preach"). Theologically, the passage reflects covenantal leadership, redefining authority as derived from proximity to Christ rather than institutional hierarchy. The study then identifies four key challenges in modern missionary work: (1) cultural and religious resistance, particularly in nations with anti-conversion laws; (2) secularization, which diminishes receptivity to institutional religion; (3) resource disparities between Global North and South missions; and (4) political hostility, as documented in persecution reports (e.g., Open Doors, 2023). Using case studies (e.g., indigenous leadership movements in Africa, hybrid discipleship models), the paper argues that Jesus’ approach offers corrective strategies. These include intentional diversity in team selection, relational discipleship amid digital evangelism, and holistic training balancing theology and praxis. The findings suggest that missionaries who emulate Jesus’ mentorship framework can cultivate resilient, contextually grounded ministries. This study contributes to missiological scholarship by bridging biblical exegesis with contemporary fieldwork, offering practical applications for churches and agencies. Further research could explore longitudinal case studies of mentorship-driven missions in restricted nations.