A transvascular system for delivering a drug to a tissue region from a blood vessel includes a catheter having a distal portion with puncturing, orientation, drug delivery, and imaging elements. The puncturing element is deployable for penetrating the vessel wall to access the tissue region. The orientation element has a predetermined relationship with the puncturing element, the imaging element detecting the location of the orientation element with respect to the tissue region to orient the puncturing element. The catheter is percutaneously introduced into the vessel, the puncturing element is oriented towards the tissue region, the puncturing element is deployed to access the tissue region, and the drug is delivered to the tissue region. An ablation device may also be deployed to create a cavity or fluid reservoir in the tissue region for receiving the drug therein, or an indwelling catheter may be advanced into and left in the tissue region.