One of the profound concepts in monotheistic religions and Islam is the culture of prayer and supplication. If the truth of prayer and its acceptance is not explained well, some ambiguities will associate certain theological discussions like the system of divine destiny and providence. In the current essay we have adopted a philosophical and rational approach to discuss the issue of acceptance of prayer in transcendent theosophy. We have focused on one of the key ambiguities, i.e. the relationship between acceptance (...) of prayer and the system of destiny and providence. In the present article we have sought to provide an analysis of the issue of acceptance of prayer and its relationship with the system of destiny and providence based on Mulla Sadra’s ontological perspective of the universe as well as his view of the hierarchy of the existential and epistemic initiation. The basic question of the current inquiry is as follows: "What kind of relationship does exist between the system of divine destiny and providence and the issue of acceptance of prayer according to the intellectual principles of Mulla Sadra?" Some of the points which have been uncovered through this research consist of: acceptance of prayer not only is not in conflict with the system of divine destiny and providence rather it is a part of this system and represents the means and medium through which the prayer reaches its destination. Prayer and its acceptance does not lie outside the causal system which is in line with the divine providence and there is a type of unity between the cause of acceptance of prayer and the Decretum Dei. Key Words: Mulla Sadra, Prayer, Destiny and Providence, Acceptance. 1. Introduction One of the revealed decrees of humans that have their origin in genesis is the issue of prayer, relationship with God and invocation to Divinity. According to this genetic and revealed law, believers ask their Lord to change their destiny through invocation to Him. On the other hand, one of the issue that is unanimously accepted by the men of faith according to monotheism is the divine providence based on which the destiny of all contingent beings is decided. 2. Problem Statement: If a good explanation is not provided for this issue it might seem to be in conflict with some other issues like the problem of prayer and its effect on the change of human destiny. For if human destiny is decided and certain according to the system of destiny and providence, then invocation and prayer will be a baseless activity. In the current essay we have sought to analyze and study the truth of acceptance of prayer as well as divine providence and the way that invocation can change the destiny and providence based on Mulla Sadra’s epistemic approach. 3. Methodology: The data for current study have been collected through library based investigations and after that they were analyzed and critically reviewed. 4. Conclusion: The following points represent the achievements of the current research on the possibility of change of human destiny and divine providence through invocation and prayer: One of the fundamental differences between human divine destiny and providence and those of other living beings is the existence of free will and volition in man. Will has a key role in human activities and can play a major role in his destiny and providence. Thus, every action which is volitional can be considered to be a part of his destiny and providence and is effective in his destiny. Accordingly, prayer is a volitional action and an effective factor in human destiny and providence. According to Mulla Sadra, the level of destiny or "Um al-Kitab" is unchangeable and is referred to also as the Protected Slate and Supreme Pen. The level of providence, size and geometry is called "Book of Elimination and Establishment" because there is a possibility of change of destiny, its elimination or establishment. In existential analysis of the issue of prayer, the acceptance of prayer does also find an existential meaning and burden according to which human request will not be necessarily and wholly realized rather in the depth of the granting of invocation and prayer the essential relationship between man and God is realized. Then, in the existential perspective of prayer, the latter is a type of human existential initiation and ascension which will be followed by human existential perfection and existential intensification in the course of acceptance. 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