Statement of the problem Health system integration has been a challenge world-wide. There is no one best model to ensure successful integration. The aim of this research is to better understand "how to" build cross-sectoral collaboration for health systems integration and transformation. This study sheds light on understanding the patterns of communication and collaboration among the participants of six newly established teams or "Tables" in one of the Local Health Integration Networks in Ontario (Canada). This naturalistic inquiry study uses a combination of Complex Adaptive Systems and Relational Coordination theories as a theoretical lens to interpret the findings. Methods A mixed-methods approach has been used with Methodological Triangulation, which includes quantitative surveys (at baseline and follow-up), qualitative interviews and member checking. Results The survey response rate was 62% at Baseline (n=45) and 25% at Follow-up (n=22). Relational Coordination Index Scores was "moderate" with no significant differences between Baseline and Follow-up and no differences between the stakeholders or "Tables." From the twelve interviews, it was revealed that context matters at the local levels. "Rural Tables" with "moderate" Relational Coordination reported "inter-dependency" and the "Suburban Tables" with "weak" Relational Coordination reported "inter-organizational challenges." Discussion There is no one-size-fits-all model for health systems integration, and there is no formula for determining whether policy directives should be "bottom-up," "top-down" or "both." Based on this conundrum, it is recommended that leaders view health care as a Complex Adaptive System in order to allow the system to transform, change and to develop inter-dependencies, inter-organizational relationships and self-organizing capacities. Policymakers should take this into consideration in policy development and evaluation. New strategies are proposed and further research is needed to inform health systems change. Conclusion The findings characterized the process of intentional cross-sectoral collaboration using Complex Adaptive Systems and Relational Coordination theories to understand the patterns of communication and collaboration among the stakeholders and "Tables". A policy framework on "how to" build cross-sectoral collaboration for health systems integration and transformation has been developed, which adds a much-needed understanding on cross-sectoral collaboration.