If you have anything similar in the list above (Few Problems), Then we should start with doing below things
Start reviewing the application design and architecture. Sometime a design change may have huge impact over the application performance. Following should be the starting reference points while reviewing the design and code of BizTalk solutions
Following are few community blogs posts which might be helpful while working with tuning & optimization.
Another important place to find a huge amount of BizTalk related articles is the TechNet Wiki itself. The best entry point is BizTalk Server Resources on the TechNet Wiki