This paper concentrates on the discussion of some contextual issues along with the challenges that are closely associated with social work practice at Macro, Mezzo and Micro levels of intervention. Here in the paper, theoretical approaches and techniques that are significantly applicable in social work practice have been presented along with some challenge-related contexts in social work practice in Bangladesh. In addition, emphasis on bio-psycho-social and spiritual aspects of clients’ problems within the framework of a holistic paradigm has been highlighted in an abridged form of description in this paper. This paper also highlights the knowledge base of social work practice including the difference between concepts and definitions of indigenous social work and general social work. It also deals with the application of the intervention process at the micro, mezzo and macro level in terms of helping the client systems with varied problems. Furthermore, social work practice challenges have also been presented in the paper which are mainly the lack of state recognition of social work as a profession, insufficient indigenous literature, inactive social work association, and standard social work education and training for the social work students and teachers.